Clinical and experimental rheumatology最新文献

Objectives: To compare two different rituximab (RTX)-based therapeutic approaches on vasculitic and lymphoproliferative-related disease activity and on non-Hodgkin lymphoma (NHL) development in a cohort of patients affected by cryoglobulinaemic vasculitis secondary to Sjögren's disease (Sjögren-CryoVasc).

Methods: Three Sjögren-CryoVasc treatment groups were identified: 1) early RTX induction followed by maintenance; 2) late RTX induction with possible on-demand retreatment; 3) no RTX treatment. The following outcomes were evaluated: a) changes in cumulative ESSDAI, considering vasculitic-related and lymphoproliferative-related domains and changes in ESSDAI specific to each single vasculitic-related and lymphoproliferative-related domain; b) development of NHL; c) occurrence of persistent hypogammaglobulinemia associated with serious infections.

Results: 13 Sjögren-CryoVasc patients were identified: 1) 5/13 treated earlier with RTX with subsequent maintenance; 2) 5/13 treated late with RTX with possible on-demand retreatment; 3) 3/13 not treated with RTX. The two RTX groups showed a decrease in the ESSDAI score with group 1 showing the most substantial reduction (p=0.028). Patients receiving RTX exhibited significant improvement in cutaneous, PNS, and articular vasculitic-related ESSDAI domains (p=0.007; p=0.006; p=0.03, respectively). By contrast RTX did not greatly affect the lymphoproliferative-related ESSDAI domains, even if an improvement was noted in the glandular and nodal domains for group 1 (p=0.03; p=0.03, respectively). No differences in NHL occurrence or safety concerns were observed among the groups.

Conclusions: RTX is an effective and safe treatment to control Sjögren-CryoVasc disease activity with a greater impact when administered earlier with a maintenance regimen. RTX alone cannot, however, affect the possible evolution of Sjögren-CryoVasc into an overt NHL.

Objectives: To assess physicians' preferences on diagnostic pathways and treatment priorities for systemic lupus erythematosus (SLE) using a discrete choice experiment (DCE).

Methods: A board of 11 SLE experts and a DCE expert statistician defined informative profiles of diagnostic pathways, pharmacological therapies, and two distinct profiles of mild-moderate and severe SLE. An independent panel of 115 clinicians involved in SLE management was invited to participate. Parameter estimates from the model were interpreted as relative preference weights (PWs). The mean PWs were used to calculate each attribute's relative importance (RI).

Results: 95 clinicians (57% females, 71% rheumatologists) completed the DCEs. The DCEs could not identify a hierarchy of importance among diagnostic pathway attributes. Nevertheless, "referral time to a rheumatologist" was considered more important for mild-moderate (RI=25%) and severe (RI=20%) SLE. Among the therapeutic attributes, the effect on organ damage progression after 12 months showed the highest preference for mild-moderate (RI=35%) and severe (RI=41%) SLE patients, followed by reduction in disease activity levels (max RI=19%) and glucocorticoid dose (max RI=13%) after six months. Reducing prednisone dose below 5 mg/day scored higher utility levels for mild-moderate (PW=66.1) than severe (PW=14.2) SLE. Administration route, action rapidity, patient-global assessment, and serious infection risk showed lesser relevance (RI 7-8%). No distinctions were found among subgroups categorised by the clinicians' areas of expertise.

Conclusions: These DCEs highlight a high degree of awareness among lupus-treating physicians, with no differences across medical specialties, of the unmet need for early diagnosis and prevention of damage accrual in SLE management.

Objectives: To evaluate self-reported physical activity (PA) levels as well as the relationship between PA, anxiety, depression, quality of life, pain, fatigue, disease activity, and organ damage in patients with idiopathic inflammatory myopathies (IIM).

Methods: All adult patients registered at the rheumatology clinic at Karolinska University Hospital in Stockholm, Sweden (2019-2022) were eligible to participate. Questionnaires measuring anxiety, depression (HADS), and PA (IPAQ) were provided during yearly check-up or by mail, due to reduced in-person visits amid the Covid-19 pandemic. Additional data was obtained from the Swedish Rheumatology Quality Registry.

Results: Of 488 invited patients, 336 agreed to participate, and 246 completed the questionnaires. Median (range) age was 64 (20-88) years, median disease duration five (0.3-61) years and two-thirds were women. Notably, 82% reported moderate/high level of PA. Probable anxiety and depression were experienced by 25% and 14%, respectively. The findings indicated a potential protective effect of PA against depression (OR 0.23, CI 0.06-0.95). Conversely, patients who were physically inactive had poorer mental health, reduced muscle function, increased organ damage, and fatigue. Fatigue demonstrated a progressive link to heightened risks of anxiety (2%, 2-4%) or depression (3%, 1-6%).

Conclusions: Most patients with IIM reported being physically active. The study highlights the potential influence of PA on mental health and its role in mitigating risks associated with depression and fatigue among IIM-patients. It also underscores the importance of patient-reported outcomes, and their role in understanding and improving healthcare interventions. Further research is needed to uncover causes and confirm these associations.

Objectives: Starting from the unmet need of early diagnosis and treatment in systemic lupus erythematosus (SLE), the study aims to explore patient preferences in diagnostic pathways and treatment modalities. It seeks to integrate clinical priorities with patient perspectives, providing an optimal approach to SLE treatment that remains uncertain.

Methods: A discrete choice experiment (DCE) has been conducted to investigate whether patient preferences align while maintaining consistent attributes and levels, providing a direct assessment of relative preferences and hypothetical treatment approaches in SLE.

Results: DCE results demonstrated that obtaining an early diagnosis is the most crucial attribute for patients. Additionally, a multidisciplinary care team, capable of enhancing clinical outcomes and patient satisfaction, is essential, along with a clinical centre conveniently located within 30 minutes of the patient's home. Lastly, patients prefer the opportunity to reduce glucocorticoid to a dosage ≤5 mg/day, and eventually discontinue, aligning with the new EULAR recommendations, and favour oral and subcutaneous routes of administration for new course of treatment.

Conclusions: Patient preferences contribute to enhancing the care pathway for SLE by optimising disease management, with a focus on multidisciplinarity and psychological support.

Objectives: To explore whether the balance of CD226 and TIGIT is disturbed in CD3+CD56-TCRαβ+CD4-CD8- (DN) T cells and have a better understanding of the potential role of DN T cells in the pathogenesis of primary Sjögren's syndrome (pSS).

Methods: The percentage of DN T cells as well as the expression of CD226 and TIGIT was identified by flowmetry. After in vitro stimulation, we further detected the expression of activation and cytotoxic marker, as well as intracellular cytokines secreted by DN T cells.

Results: DN T cells were found to expand in the peripheral blood of pSS patients (1.77±0.66%) and correlate with IgG (r=0.451, p<0.05), C3 (r=-0.438, p<0.05) and C4 (r=-0.470, p<0.05). Imbalanced CD226/TIGIT was observed on peripheral DN T cells of pSS patients, especially the overexpression of inhibitory immunoreceptor TIGIT. The expression ratio of TIGIT and CD226 on DN T cells was elevated in pSS patients and correlated with ESSDAI scores≥5 (r=0.743, p<0.05). Besides, these DN T cells were found to be activated and show strong cytotoxicity.

Conclusions: The balance between CD226 and TIGIT on DN T cells was disturbed and correlated with the disease activity in pSS patients, which may be implicated in the pathogenesis of pSS.

Objectives: Evidence regarding the efficacy of neridronate in the treatment of complex regional pain syndrome type I (CRPS I) is increasing, however, very little data are available in paediatric age. Our aim was to analyse the safety and the efficacy of neridronate in a case series of children with CRPS I, according to the Budapest criteria, who did not respond to previous pharmacological and physical therapy.

Methods: We collected data of children affected by CRPS I from three paediatric rheumatology centres who received neridronate. Efficacy was evaluated by changes in pain intensity, vasomotor changes, physical function, need for pain medications and MRI findings. Adverse effects were also documented.

Results: Five children (3 females and 2 males, mean age 10.4 years, range 7-13 years) who received neridronate (4 intravenous, 1 intramuscular) were included. All patients had failed previous medical treatments (NSAIDs in 4, local steroids in 2, gabapentin, vitamin D and calcium supplementation in 1) and non-medical therapies (physiotherapy in 4, magnetotherapy in 2, laser in 1). Four out of five patients reported a significant improvement in pain (average VAS pre-treatment 9.6, post-treatment 2.6), recovery of physical function, and a reduced need for pain medications. Before treatment, all patients underwent MRI which revealed bone oedema that disappeared in the three of them after treatment. Neridronate was well-tolerated as only one patient experienced mild flu-like symptoms.

Conclusions: Our data suggest that in children as in adults with CRPS I, neridronate may represent an effective and safe treatment option, particularly in those who do not respond to other pain treatments.

Objectives: To explore the effectiveness of tofacitinib for immunoglobulin G4-related disease (IgG4-RD) and idiopathic retroperitoneal fibrosis (IRF), and investigate the expression of JAKs in the lesion of these diseases.

Methods: Clinical data of patients with IgG4-RD or IRF who were administered with tofacitinib monotherapy were collected. IgG4-RD responder index (IgG4-RD RI) was assessed. The expression of JAK1, JAK2, JAK3, and TYK2 were analysed with immunohistochemistry staining in three salivary glands specimens of IgG4-RD and one retroperitoneal tissue of IRF.

Results: Two patients with IRF and two patients with IgG4-RD used tofacitinib monotherapy. Two patients with IRF achieved complete remission with diminished retroperitoneal mass and decreased CRP, as IgG4-RD RI decreased from 6 to 1 in both of them. One with IgG4-RD achieved complete remission with alleviated enlargement of pancreas and IgG4 level decreased from 13.7 g/L to 2.4 g/L, as IgG4-RD RI decreased from 12 to 1. One with IgG4-RD achieved partial response with IgG4 level decreased from 77.1g/L to 25.8g/L as IgG4-RD RI from 18 to 6. JAK1, JAK2, JAK3, and TYK2 expression were detected in biopsy tissues. The staining intensity of the JAK family on the lesion from one IRF patient was similar to those from IgG4-RD patients.

Conclusions: Tofacitinib is a potentially effective treatment for IgG4-RD and IRF and it is reasonable to conduct clinical trial to validate its efficacy. The JAKs were expressed in the inflammatory lesions of IgG4-RD and IRF and they may share a common pathogenesis pathway that is independent of IgG4 production.