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Objectives: To measure the association between SLE remission and scores of patients-reported outcome (PRO) measures., Methods: We performed a prospective cohort study of SLE patients with a 2-year follow-up, using Lupus Patient-Reported Outcome (LupusPRO), Lupus Quality of Life (LupusQoL), Systemic Lupus Erythematosus Quality of Life (SLEQOL) and 36-item Short Form (SF-36) questionnaires. Remission was defined as remission off treatment (ROFT) and remission on treatment (RONT) according to the definitions of remission in SLE consensus. Mixed models accounting for repeated measures were used to compare groups as follow: ROFT and RONT vs no remission and lupus low disease activity state (LLDAS) vs no LLDAS., Results: A total of 1478 medical visits and 2547 PRO questionnaires were collected during the follow-up from the 336 recruited patients. A between-group difference in PRO scores reaching at least 5 points on a 0-100 scale was obtained in the following domains: lupus symptoms (LLDAS: +5 points on the 0-100 scale, RONT: +9, ROFT: +5), lupus medication (LLDAS: +5, RONT: +8, ROFT: +9), pain vitality (LLDAS: +6, RONT: +9, ROFT: +6) of LupusPRO; role emotional (LLDAS: +5, RONT: +8), role physical (RONT: +7 and ROFT: +7), bodily pain (RONT: +6), mental health (RONT: +5) and social functioning (RONT: +6) of SF-36. In contrast, a between-group difference reaching at least 5 points was not achieved for any of the LupusQoL and SLEQOL domains., Conclusions: RONT, ROFT and LLDAS were associated with significant and clinically relevant higher QoL in most PRO domains of the LupusPRO (disease specific) and SF-36 (generic) questionnaires, but not with LupusQoL and SLEQOL disease-specific questionnaires., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Mediation analyses were conducted to measure the extent to which musculoskeletal (MSK) flares and depression affected physical health through excessive fatigue., Methods: Mediation analyses were performed in a large multicentre cohort of SLE patients. Domains of the LupusQoL and SLEQOL questionnaires were selected as outcomes, MSK flares according to the SELENA-SLEDAI flare index (SFI-R) score and depression defined by Center for Epidemiologic Studies-Depression scale (CES-D) scale as exposures and different fatigue domains from MFI-20 and LupusQoL questionnaires as mediators. For each model, total, direct, indirect effects and proportion of effect mediated by fatigue (i.e. proportion of change in health-related quality of life) were determined., Results: Of the 336 patients, 94 (28%) had MSK flares at inclusion and 99 (29.5%) were considered with depression. The proportion of the total effect of MSK flares on physical health impairment explained by fatigue ranged from 59.6% to 78% using the LupusQOL 'Physical health' domain and from 51.1% to 73.7% using the SLEQOL 'Physical functioning' domain, depending on the fatigue domain selected. The proportion of the total effect of depression on physical health impairment explained by fatigue ranged from 68.8% to 87.6% using the LupusQOL 'Physical health' domain and from 79.3% to 103.2% using the SLEQOL 'Physical functioning' domain, depending on the fatigue domain selected., Conclusions: The effect of MSK flares and depression on physical health impairment is largely mediated by fatigue. Thus, the patient's perception of disease activity as measured by physical health is largely influenced by fatigue. In addition, fatigue has a significant negative impact on quality of lifeof SLE patients with depression., Trial Registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01904812., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To describe the characteristics, treatment and outcome of patients with immune thrombocytopenia with clinical significance (ITPCS) associated with SLE., Methods: This retrospective multicentre study included SLE patients who experienced ≥1 ITPCS (defined as ITP with attributable bleeding disorders and/or a platelet count <30×109/l). Other causes of secondary thrombocytopenia were excluded. Major bleeding event (MBG) was defined as Khellaf score >8 and/or WHO score >2., Results: A total of 90 patients were included, the median (range) follow-up duration was 80 (6-446) months. ITP was diagnosed before SLE in 25 patients. They presented a high rate of autoimmune haemolytic anaemia (15%), antiphospholipid antibody (62%) and antiphospholipid syndrome (19%). The 25 (28%) patients who experienced MBG had significantly more bleedings at ITP diagnosis and higher bleeding scores, and serositis and thrombosis during follow-up. They required significantly more treatment lines, transfusions and hospitalizations. The 11 (12%) patients who experienced no bleeding event presented a significantly more restricted SLE phenotype (cutaneous and/or articular). Patients received a mean (range) of 4.2 (1-11) treatment lines. Corticosteroids and HCQ allowed ITPCS overall response in one-third of patients. The median relapse-free survival of rituximab (n = 34), AZA (n = 19), MMF (n = 8), thrombopoietin-receptor agonists (n = 16) and splenectomy (n = 19) were 53, 31.5, 61, 24.5 and 78 months, respectively. Four patients experienced thrombotic events after splenectomy and one occurred under thrombopoietin-receptor agonist treatment., Conclusion: SLE-ITCS patients displayed a high rate of haematological abnormalities and MBG patients exhibited higher morbidity. Management of thrombocytopenia was highly heterogeneous and many options seem viable., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The course of cryoglobulinaemia varies widely, from asymptomatic patients to severe vasculitis syndrome. Renal involvement (RI) is the major prognostic factor, and frequently occurs several years after diagnosis. However, predictive factors for RI are not well known. The aim of our study was to identify RI predictive factors during cryoglobulinaemia., Methods: We retrospectively reviewed the clinical charts of a consecutive series of 153 patients positive for cryoglobulinaemia in the University Hospital of Lyon (France). RI was defined either histologically or biologically if cryoglobulinaemia was the only possible cause of nephropathy., Results: Among the 153 positive patients (mean age 55 years, 37% male), cryoglobulinaemia was associated with RI in 45 (29%) patients. Sixty-five percent of patients had Type II cryoglobulinaemia, 28% had Type III and 7% had Type I. Autoimmune diseases were the most common aetiology (48%), followed by infectious diseases (18%) and lymphoproliferative disorders (13%). Membranoproliferative glomerulonephritis was the main histological pattern (93% of the 14 histological analyses). A multivariable logistic regression showed that Type II cryoglobulinaemia, a high serum cryoglobulin concentration, the presence of an IgG kappa monoclonal component and diabetes were independently associated with the risk for developing RI., Conclusion: We identified several factors predictive of RI in patients with cryoglobulinaemia, which were different from the diagnostic criteria for cryoglobulinaemic vasculitis. This could suggest a specific pathophysiology for RI. We suggest performing an extensive renal monitoring and ensure nephroprotection when a diagnosis of cryoglobulinaemia is made in patients with these predictive factors.

Objectives: FMF is the most frequent autoinflammatory disease and is associated in most patients with bi-allelic MEFV mutations. MEFV encodes Pyrin, an inflammasome sensor activated following RhoGTPase inhibition. The functional consequences of MEFV mutations on the ability of Pyrin variants to act as inflammasome sensors are largely unknown. The aim of this study was to assess whether MEFV mutations affect the ability of Pyrin to detect RhoGTPase inhibition and other inflammasome stimuli., Methods: IL-1β and IL-18 released by monocytes from healthy donors (HDs) and FMF patients were measured upon specific engagement of the Pyrin, NLRP3 and NLRC4 inflammasomes. Cell death kinetics following Pyrin activation was monitored in real time., Results: Monocytes from FMF patients secreted significantly more IL-1β and IL-18 and died significantly faster than HD monocytes in response to low concentrations of Clostridium difficile toxin B (TcdB), a Pyrin-activating stimulus. Monocytes from patients bearing two MEFV exon 10 pathogenic variants displayed an increased Pyrin inflammasome response compared with monocytes from patients with a single exon 10 pathogenic variant indicating a gene-dosage effect. Using a short priming step, the response of monocytes from FMF patients to NLRP3- and NLRC4-activating stimuli was normal indicating that MEFV mutations trigger a specific hypersensitivity of monocytes to low doses of a Pyrin-engaging stimulus., Conclusion: Contrary to the NLRP3 mutations described in cryopyrin-associated periodic syndrome, FMF-associated MEFV mutations do not lead to a constitutive activation of Pyrin. Rather, FMF-associated mutations are hypermorphic mutations that specifically decrease the activation threshold of the Pyrin inflammasome without affecting other canonical inflammasomes., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)