成人発症スチル病

Adult-onset Still's disease (AOSD) is a rare, systemic autoinflammatory disorder predominantly affecting young adults. It is characterized by polyarthritis, systemic inflammation with high spiking fevers, a transient salmon-pink rash, hepatosplenomegaly, and elevated ferritin levels. Its clinical presentation is highly heterogeneous and lacks specificity, and there are currently no unified diagnostic criteria. Differential diagnosis requires the exclusion of infections, malignancies, other rheumatic diseases, and adverse drug reactions. We report the case of a woman in her 80s in whom the diagnosis of adult-onset Still's disease was delayed owing to her advanced age, atypical rash, and positive antinuclear antibody status, despite significantly elevated serum ferritin levels. This case highlights that AOSD can affect older individuals, including those aged ≥ 80 years, and should be considered in the differential diagnosis of these patients when presenting with unexplained fever, especially if accompanied by rashes and hyperferritinemia. Moreover, a positive antinuclear antibody test does not rule out the diagnosis of AOSD. Timely and appropriate treatment can improve the prognosis of older patients with adult-onset Still's disease.

OBJECTIVE: Information is limited on the natural history and current treatment patterns in macrophage activation syndrome (MAS), a life-threatening hyperinflammatory syndrome complicating Still's disease (systemic juvenile idiopathic arthritis [sJIA] and adult-onset Still's disease [AOSD]). AMETHYST aimed to describe real-world treatment patterns and outcomes in glucocorticoid (GC)-refractory MAS complicating Still's disease. METHODS: In this retrospective cohort study, medical data from January 1, 2012, to March 31, 2023, were abstracted from charts of all eligible patients across eight sites in Europe, Canada, and the US for index MAS episodes (occurring between January 1, 2012, and September 30, 2022, and meeting eligibility criteria). RESULTS: Overall, 55/64 (86%) included patients had sJIA and 9/64 (14%) had AOSD. Most patients (53/64 [82.8%]) were children at index (median age: 7.0 years). MAS was characterized by rash (60.4%), fever (52.8%), and hepatic involvement (49.1%). All patients received GCs; most were also treated with anakinra (48/64 [75%]) and/or ciclosporin (33/64 [51.6%]). Normalization of 7 (complete MAS laboratory remission) or ≥3 (partial remission) prespecified laboratory parameters occurred in 7/64 (10.9%) and 41/64 (64.1%) patients, respectively. GCs were tapered in 50/64 (78.1%) patients (median: 39.9 days). Per investigator assessment of clinical signs/symptoms for the index MAS episode, 24/64 (37.5%) and 26/64 (40.6%) patients had a complete and partial response, respectively. MAS recurred in 20/64 (31.3%) patients. There were 7/64 (10.9%) deaths; estimated 1-year survival probability was 93.75%. CONCLUSIONS: Low MAS laboratory remission rates and toxicities of high-dose GCs combined with other treatments highlight the need for safer, more effective therapies.

OBJECTIVE: To comparatively evaluate recent adult-onset Still's disease (AOSD) activity measures-Development and Validation of Disease Activity in AOSD (DAVID), Still's Disease Activity Score (SDAS), Still Activity Score (SAS) with Pouchot's Systemic Score (PSS) in an independent multicentre cohort. METHODS: DAVID and SDAS were modified (m) by omitting global assessments due to availability and to circumvent incorporation bias. Criterion validity was assessed by receiver operating characteristic (ROC) analysis against the treating physician's determination of disease activity (active vs inactive). Responsiveness was evaluated by comparing mean change in scores between remission and active disease, and Cohen's d. Longitudinal sensitivity to change was assessed using linear mixed-effects models with z-standardised scores and marginal R². Primary analysis uses imputed data, with complete-case sensitivity analysis. RESULTS: The cohort comprised 86 patients with initially active AOSD (64% female; mean age 39.4±15.0 years). In ROC analyses, mSDAS, mDAVID and SAS showed comparable area under the curves (0.69, 0.68 and 0.68, respectively), whereas PSS had a lower AUC (0.60). Responsiveness was greatest for mDAVID (Cohen's d 0.76 (95% CI 0.30 to 1.20)), followed by mSDAS (0.61 (0.13 to 1.1)), SAS (0.46 (-0.01 to 0.90)) and PSS (0.22 (-0.30 to 0.68)). Longitudinal sensitivity to change, quantified by marginal R², was highest for mDAVID (0.65 (95% CI 0.59 to 0.70)), followed by mSDAS (0.61 (0.55 to 0.67)), PSS (0.61 (0.54 to 0.67)) and SAS (0.55 (0.45 to 0.64)). Sensitivity analyses using complete cases yielded similar results. CONCLUSION: mDAVID and mSDAS demonstrated the most favourable and largely comparable performance profiles across the evaluated metrics, with mDAVID showing greater responsiveness and mSDAS demonstrating a stronger correlation with the articular disease domain. TRIAL REGISTRATION NUMBER: ISRCTN86135778.

Elevated serum immunoglobulin G4 (IgG4) levels have been reported in various rheumatic diseases; however, the factors associated with IgG4 elevation remain incompletely understood. This study aimed to evaluate the frequency of elevated serum IgG4 in different rheumatic diseases and to explore its association with disease classification based on typical inflammatory characteristics and autoantibody status. This retrospective single-center study included 255 patients with rheumatic diseases who underwent serum IgG4 testing between January 2017 and December 2022. Patients were categorized for exploratory disease-level analyses according to their typical association with elevated C-reactive protein (CRP) levels (rheumatoid arthritis [RA], spondyloarthritis, vasculitis, and adult-onset Still disease) or without prominent CRP elevation (Sjögren syndrome, systemic lupus erythematosus, retroperitoneal fibrosis, idiopathic inflammatory myopathy, and undifferentiated connective tissue disease), as well as according to the presence or absence of disease-specific autoantibodies. The frequency of elevated serum IgG4 (≥1.35 g/L) was compared between groups. Elevated IgG4 was more frequently observed in patients with RA than in those with Sjögren syndrome (30.36% vs 11.83%, P = .005). Rheumatic diseases classified as CRP-associated demonstrated a higher frequency of elevated IgG4 than non-CRP-associated diseases (30.23% vs 14.20%, P < .001). Among patients with RA, elevated IgG4 was associated with higher levels of immunoglobulin M, immunoglobulin G, CRP, erythrocyte sedimentation rate, and Disease Activity Score 28-CRP scores (all P < .05). In this retrospective cohort, elevated serum IgG4 was more frequently observed in rheumatic diseases classified as CRP-associated than in non-CRP-associated diseases. No significant association was observed between elevated serum IgG4 frequency and autoantibody status. These findings demonstrate an association between disease classification based on typical inflammatory characteristics and the frequency of elevated serum IgG4; however, prospective studies incorporating patient-level inflammatory assessments are required to determine the clinical significance of this association.

OBJECTIVES: To validate the diagnostic performance of the HScore for Still's disease (SD)-associated macrophage activation syndrome (MAS; SD-MAS) in adults compared with those of the HLH-2004 diagnostic criteria used with modifications (HLH-04) and the 2016 EULAR/ACR/PRINTO classification criteria for systemic juvenile idiopathic arthritis-associated MAS (MAS-2016). METHODS: This multicentre case-control study, conducted at three medical centres in Japan between 2004 and 2023, enrolled patients ≥16 years with active SD and allocated them into SD without MAS and SD-MAS groups by an expert panel. For each patient, we calculated the HScore, HLH-04, MAS-2016 and modified HScore, which excluded haemophagocytosis on bone marrow aspirate. Receiver operating characteristic curve analysis was used to assess the discriminative ability of each criterion. Logistic regression analysis was performed separately for 'model-1' (HScore and HLH-04) and 'model-2' (MAS-2016 and modified HScore). RESULTS: This study included 86 patients with SD, 25 of whom had SD-MAS. The HScore showed the best area under the curve at 0.991 (95% CI 0.977-1.000), with a cut-off value of 192 (sensitivity, 96.0%; specificity, 96.7%). The optimal cut-off for the modified HScore was 171 (sensitivity, 92.0%; specificity, 83.6%). Multivariate analysis identified only the HScore in model-1 [odds ratio (OR) 1.271; 95% CI 1.006-1.606], whereas both MAS-2016 (OR 4.249; 95% CI 1.636-11.041) and modified HScore (OR 1.066; 95% CI 1.017-1.118) were identified in model-2. CONCLUSIONS: The HScore and modified HScore could be useful tools for diagnosing SD-MAS in adults with and without bone marrow aspiration, respectively.