Background Various observations have suggested that the course of COVID-19 might be less favourable in patients with inflammatory rheumatic and musculoskeletal diseases receiving rituximab compared with those not receiving rituximab. We aimed to investigate whether treatment with rituximab is associated with severe COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases.Methods In this cohort study, we analysed data from the French RMD COVID-19 cohort, which included patients aged 18 years or older with inflammatory rheumatic and musculoskeletal diseases and highly suspected or confirmed COVID-19. The primary endpoint was the severity of COVID-19 in patients treated with rituximab (rituximab group) compared with patients who did not receive rituximab (no rituximab group). Severe disease was defined as that requiring admission to an intensive care unit or leading to death. Secondary objectives were to analyse deaths and duration of hospital stay. The inverse probability of treatment weighting propensity score method was used to adjust for potential confounding factors (age, sex, arterial hypertension, diabetes, smoking status, body-mass index, interstitial lung disease, cardiovascular diseases, cancer, corticosteroid use, chronic renal failure, and the underlying disease [rheumatoid arthritis vs others]). Odds ratios and hazard ratios and their 95% CIs were calculated as effect size, by dividing the two population mean differences by their SD. This study is registered with ClinicalTrials.gov, NCT04353609.
Naive monoclonal T cells specific for the male antigen can be stimulated in vivo to eliminate male cells and become memory cells or to permit survival of male cells and become tolerant. Memory cells responded to TCR ligation by cyclic oscillations of calcium levels and immediate secretion of very high levels of IL-2 and interferon-gamma. Tolerant cells did not proliferate in response to ionomycin and phorbol myristate acetate, failing to mobilize calcium to produce IL-2 or express IL-2R, but survived for long time periods in vivo and secreted IL-10. These results emphasize that tolerance is not an absence of all functional activity and may be associated with modifications of behavior conferring important regulatory functions on tolerant T cells.
Objective. To describe the long-term outcome and determine predictors of severity among patients with oligoarticular-onset juvenile idiopathic arthritis (JIA).Methods. In a longitudinal study, 207 patients with oligoarticular-onset JIA who were referred between 1988 and 1998 were evaluated. At disease onset, selected clinical and laboratory data were collected as independent variables. A polyarticular disease course, joint erosion, uveitis, and remission were assessed as dependent variables. Longitudinal analyses were performed with the Kaplan-Meier method, and multivariate analysis with the Cox model.Results. After 6 years of followup, the probability of a polyarticular course of disease was 50%, joint erosion was 35%, uveitis was 30%, and remission was 23% in these patients. Joint erosion was strongly associated with a polyarticular course. A high erythrocyte sedimentation rate (ESR) as well as involvement of more than 1 joint or involvement of an upper limb at disease onset were predictors of disease extension. A high ESR was also a strong predictor of a destructive course, and a family history of psoriasis was predictive of uveitis occurrence. No predictive factor for remission could be identified.Conclusion. Oligoarticular-onset JIA is a severe disease with frequent complications. Factors predictive of severity in oligoarticular-onset JIA were identified. This could allow early identification of high-risk patient subgroups, warranting a more aggressive therapeutic approach.
Objectives The aim of this study was to investigate whether the quadrivalent human papillomavirus (HPV) vaccine Gardasil is associated with a change in the risk of autoimmune disorders (ADs) in young female subjects. Design Systematic case–control study of incident ADs associated with quadrivalent HPV vaccination in young women across France. Participants and setting A total of 113 specialised centres recruited (from December 2007 to April 2011) females aged 14–26 years with incident cases of six types of ADs: idiopathic thrombocytopenic purpura (ITP), central demyelination/multiple sclerosis (MS), Guillain–Barré syndrome, connective tissue disorders (systemic lupus erythematosus, rheumatoid arthritis/juvenile arthritis), type 1 diabetes mellitus and autoimmune thyroiditis. Control subjects matched to cases were recruited from general practice. Analysis Multivariate conditional logistic regression analysis; factors included age, geographical origin, smoking, alcohol consumption, use of oral contraceptive(s) or vaccine(s) other than Gardasil received within 24 months before the index date and personal/family history of ADs. Results Overall, 211 definite cases of ADs were matched to 875 controls. The adjusted odds ratio (OR) for any quadrivalent HPV vaccine use was 0.9 [95% confidence interval (CI) 0.5–1.5]. The individual ORs were 1.0 (95% CI 0.4–2.6) for ITP, 0.3 (95% CI 0.1–0.9) for MS, 0.8 (95% CI 0.3–2.4) for connective disorders and 1.2 (95% CI 0.4–3.6) for type 1 diabetes. No exposure to HPV vaccine was observed in cases with either Guillain–Barré syndrome or thyroiditis. Conclusions No evidence of an increase in the risk of the studied ADs was observable following vaccination with Gardasil within the time periods studied. There was insufficient statistical power to allow conclusions to be drawn regarding individual ADs.
Exposure to HPV vaccines was not associated with an increased risk of ADs within the time period studied. Results were robust to case definitions and time windows of exposure. Continued active surveillance is needed to confirm this finding for individual ADs.
Juvenile systemic lupus erythematosus (JSLE) represents 15-20% of all SLE cases. The leading presenting symptoms of JSLE are constitutional and not specific such as fatigue, headache, weight loss or mood swings. They are also encountered in healthy adolescents, which explains frequent diagnosis delay. The frequency of irreversible damage is high in JSLE and involves especially the renal, musculoskeletal and neuropsychiatric systems. Although the overall prognosis has markedly improved, thanks to earlier diagnosis and new therapeutic approaches, cardiovascular, hematological events and chronic renal failure remain severe, and constitute the main disease-related causes of death. Treatment is based on hydroxycloroquine and corticosteroids. Immunosuppressive agents must be discussed to decrease the duration of corticosteroids use. New drugs and monoclonal antibodies targeting B-cells and B-cell related cytokines are being evaluated with encouraging results. Management of JSLE has to challenge three objectives: controlling disease progression, obtaining patient's adherence to treatment, and preventing consequences of medication side effects on growth, puberty, development and fertility. Patients' quality of life and psychosocial development have also to be taken into account, as well as the organization of a successful transition from paediatric to adult care.
Multicentric Castleman Disease (MCD) is an idiopathic lymphoproliferative disorder, reported exceptionally in children and generally believed to be an autoinflammatory disease resulting in an increase of interleukin-6 secretion. Previous studies in adult patients suggested a beneficial role of the anti-interleukin-6 receptor antibody tocilizumab on the clinical and biologic disease manifestations of MCD. Here, we describe the efficacy and safety of tocilizumab in two children with MCD, which was diagnosed on the basis of clinical and histologic findings. In both cases, tocilizumab was administered intravenously at a dose of 8 mg/kg every 2 weeks. The tocilizumab treatment alleviated fever and restored growth rate in both patients. The patients' hypergammaglobulinemia, high C-reactive protein, and high erythrocyte sedimentation rates normalized simultaneously. Nevertheless, splenomegaly persisted in the first patient, and a secondary hepatic node appeared in the second patient. The side effects, essentially sustained thrombocytopenia, were mild in both cases. For the first patient, following an initial 10-month period, the interval between infusions was increased. This patient benefited from sustained remission for a period of 3 years. Tocilizumab was effective and safe in these two children with MCD.
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