Still's disease continuum from childhood to elderly: data from the international AIDA Network Still's disease registry.

OBJECTIVE: Still's disease is more frequently observed in the paediatric context, but a delayed onset is not exceptional both in the adulthood and in the elderly. However, whether paediatric-onset, adult-onset and elderly-onset Still's disease represent expressions of the same disease continuum or different clinical entities is still a matter of controversy. The aim of this study is to search for any differences in demographic, clinical features and response to treatment between pediatric-onset, adult-onset and elderly-onset Still's disease. METHODS: Subjects included in this study were drawn from the International AutoInflammatory Disease Alliance Network registry for patients with Still's disease. RESULTS: A total of 411 patients suffering from Still's disease were enrolled; the disease occurred in the childhood in 65 (15.8%) patients, in the adult 314 (76.4%) patients and in the elderly in 32 (7.8%) patients. No statistically significant differences at post-hoc analysis were observed in demographic features of the disease between pediatric-onset, adult-onset and elderly-onset Still's disease. The salmon-coloured skin rash (p=0.004), arthritis (p=0.009) and abdominal pain (p=0.007) resulted significantly more frequent among paediatric patients than in adult cases, while pleuritis (p=0.015) and arthralgia (p<0.0001) were significantly more frequent among elderly-onset patients compared with paediatric-onset subjects. Regarding laboratory data, thrombocytosis was significantly more frequent among paediatric patients onset compared with adult-onset subjects (p<0.0001), while thrombocytopenia was more frequent among elderly-onset patients although statistical significance was only bordered. No substantial differences were observed in the response to treatments. CONCLUSIONS: Despite some minor difference between groups, overall, demographic, clinical, laboratory and treatments aspects of Still's disease were similarly observed in patients at all ages. This supports that pediatric-onset, adult-onset and elderly-onset Still's disease is the same clinical condition arising in different ages.

Derivation and validation of four patient clusters in Still's disease, results from GIRRCS AOSD-study group and AIDA Network Still Disease Registry.

BACKGROUND: Different patient clusters were preliminarily suggested to dissect the clinical heterogeneity in Still's disease. Thus, we aimed at deriving and validating disease clusters in a multicentre, observational, prospective study to stratify these patients. METHODS: Patients included in GIRRCS AOSD-study group and AIDA Network Still Disease Registry were assessed if variables for cluster analysis were available (age, systemic score, erythrocyte sedimentation rate (ESR), C reactive protein (CRP) and ferritin). K-means algorithm with Euclidean metric and Elbow plot were used to derive an adequate number of clusters. RESULTS: K-means clustering assessment provided four clusters based on means standardised according to z-scores on 349 patients. All clusters mainly presented fever, skin rash and joint involvement. Cluster 1 was composed by 115 patients distinguished by lower values of age and characterised by skin rash myalgia, sore throat and splenomegaly. Cluster 2 included 128 patients identified by lower levels of ESR, ferritin and systemic score; multiorgan manifestations were less frequently observed. Cluster 3 comprised 31 patients categorised by higher levels of CRP and ferritin, they were characterised by fever and joint involvement. Cluster 4 contained 75 patients derived by higher values of age and systemic score. Myalgia, sore throat, liver involvement and life-threatening complications, leading to a high mortality rate, were observed in these patients. CONCLUSIONS: Four patient clusters in Still's disease may be recognised by a multidimensional characterisation ('Juvenile/Transitional', 'Uncomplicated', 'Hyperferritinemic' and 'Catastrophic'). Of interest, cluster 4 was burdened by an increased rate of life-threatening complications and mortality, suggesting a more severe patient group.

Long-term Efficacy of Interferon-Free Antiviral Treatment Regimens in Patients With Hepatitis C Virus-Associated Cryoglobulinemia Vasculitis.

BACKGROUND & AIMS: In small-size and short-term studies of hepatitis C virus-associated cryoglobulinemia vasculitis (HCV-CryoVas), patients had a higher rate of response and tolerance to direct-acting antiviral (DAA) agents than interferon-containing regimens. We collected follow-up data from a clinical trial to determine the long-term effectiveness and tolerance of all-oral, interferon-free DAA regimens in patients with CryoVas. METHODS: We collected follow-up data from a prospective international multicenter cohort study of 148 patients with symptomatic HCV-CryoVas (53.7% with cirrhosis and 49.3% naive to treatment with DAAs). All patients received DAA (sofosbuvir plus daclatasvir, n = 53; sofosbuvir plus ribavirin, n = 51; sofosbuvir plus ledipasvir, n = 23; or sofosbuvir plus simeprevir, n = 18), for 12 or 24 weeks, from 2014 through 2017; the median follow-up time was 15.3 months. A complete clinical response was defined as improvement of all organs involved at baseline and the absence of clinical relapse; a partial response was defined as improvement in some but not all organs involved at baseline. The primary end point was clinical response of CryoVas symptoms at week 12 after stopping DAA therapy. RESULTS: A complete response was reported for 106 patients (72.6%), a partial response for 33 patients (22.6%), and no response for 7 patients (4.8%). Cryoglobulins were no longer detected in blood samples from 53.1% of patients, and 97.2% of the patients had a sustained virologic response to therapy. Premature DAA withdrawal was reported for 4.1% of patients. Factors associated with no or partial response to therapy included a severe form of CryoVas (odds ratio, 0.33; 95% CI, 0.12-0.91; P = .03) and peripheral neuropathy (odds ratio, 0.31; 95% CI, 0.11-0.84; P = .02). After a median follow-up time of 15.3 months, 4 patients (2.8%) died. The CryoVas manifestation of purpura was cleared from 97.2% of patients, renal involvement from 91.5% of patients, arthralgia from 85.7% of patients, neuropathy from 77.1% of patients, and cryoglobulinemia from 52.2%. CONCLUSIONS: In a long-term follow-up analysis of data from a clinical trial, we found that more than 95% of patients with HCV-CryoVas have a full or partial response of symptoms to different DAA treatment regimens. Fewer than 5% of patients stop therapy prematurely and less than 3% die. A severe form of CryoVas and peripheral neuropathy were associated with a lack of response of HCV-CryoVas to DAA therapy.