The European Alliance of Associations for Rheumatology recommendations for cardiovascular risk management highlighted the importance of traditional cardiovascular risk factor control in antiphospholipid syndrome (APS). However, cardiovascular risk factor target attainment in APS and differences between primary APS and systemic lupus erythematosus (SLE)-related APS remain uncertain. Cardiovascular risk factor data were collected from medical records of patients in 17 centres from 11 countries between Jan 1, 2015, and Jan 1, 2020 (extended to 2022 for some centres unable to complete the survey by the end of 2020 due to the COVID-19 pandemic), and analysed cross-sectionally. Included patients were 18 years or older and met the revised Sapporo APS classification criteria. Patients who also met the 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE were classified as having SLE-related APS. Patients with APS in association with systemic autoimmune diseases other than SLE were excluded. Cardiovascular risk was estimated using the Systematic Coronary Risk Evaluation algorithm, and cardiovascular risk factor target attainment was assessed using European Society of Cardiology guidelines. Unadjusted and adjusted mixed effects logistic regression models were fitted. People with lived experience were not involved in the study design. In total, 1003 patients with APS were included (779 [78%] women and 224 [22%] men; 662 [66%] of 1000 were White), with a median age of 47·0 years (IQR 38·0-57·0) and a median disease duration of 11·0 years (5·0-18·0). 539 (54%) patients had primary APS and 464 (46%) had SLE-related APS. We found a high prevalence of cardiovascular risk factors (hypertension, 411 [41%] of 1003; hyperlipidaemia, 344 [34%] of 1003; obesity, 295 [32%] of 919; current smoking, 186 [19%] of 963) and inadequate individual (blood pressure less than 130/80 mm Hg, BMI, and lipids) and composite cardiovascular risk factor control in all patients. A higher prevalence of hypertension (234 [50%] of 464 vs 177 [33%] of 539; p<0·0001) and hyperlipidaemia (184 [40%] of 464 vs 160 [30%] of 539; p=0·0009) was observed in SLE-related APS versus primary APS, but a lower prevalence of current smoking (72 [16%] of 452 vs 114 [22%] of 511; p=0·012). Patients with primary APS had worse target attainment for smoking cessation (397 [78%] of 511 vs 380 [84%] of 452; p=0·012), blood pressure less than 130/80 mm Hg (246 [48%] of 514 vs 258 [57%] of 456; p=0·0067), and two or more cardiovascular risk factor targets (of smoking, BMI, blood pressure, LDL) than patients with SLE-related APS in the entire group, as well as worse target attainment for smoking cessation, blood pressure less than 130/80 mmHg, BMI, LDL, triglycerides, two or more and three or more targets in the high and very high cardiovascular risk subgroup. Age and arterial thrombosis history were associated with lower odds of attaining three or more or all four cardiovascular risk factor targets. In this large real-world study, high prevalence and suboptimal cardiovascular risk factor control were observed in patients with APS, highlighting the need for increased cardiovascular risk awareness, especially in those with primary APS, whose cardiovascular risk is often overlooked. None.

Giant cell arteritis (GCA), also called as temporal arteritis, is a systemic vasculitis, primary affecting individuals over 50 years of age and mostly women. The disease can manifest with symptoms of systemic inflammatory response syndrome as well with symptoms of systemic vasculitis affecting mainly medium and large vessels, including branches of the carotid artery, first of all the ophthalmic and temporal. Pathogenetically, arterial damage in GCA is a combination of autoinflammatory and autoimmune processes, resulting in vascular wall remodeling with narrowing of the arterial lumen and subsequent ischemia in the affected organs and tissues. One of the uncommon symptoms of GCA, which in some cases may precede the onset of the disease, is cochleovestibular dysfunction, in particular sensorineural hearing loss, which might occur in 25-60% of GCA cases. The clinical case of untypical GCA was shown. The disease manifested after SARS-Cov-2 infection as the subacute rhinosinusitis and bilateral otitis media with effusion that finally resulted in profound mixed hearing loss. The clinical features of the disease looked like granulomatosis with polyangiitis, however, no increase in antinuclear and antineutrophil cytoplasmic antibody levels was detected. A specific clinical feature with unilateral vision loss after 12 months from the disease onset could help to verify it. Urgently corticosteroid therapy let us relieve both main symptoms and rhinosinusitis with bilateral otitis media with effusion that resulted in significant hearing improvement. It has been suggested that the combination of middle and inner ear lesions in this case could either be a consequence of the simultaneous development of GPA and GCA, or was the result of coincidence of a number of their pathogenesis links, specifically the activation of B cells, as well as excessive proliferation of monocytes/macrophages producing metalloproteinase-9. Гигантоклеточный артериит (ГКА, болезнь Хортона, височный артериит) — системный васкулит, поражающий главным образом лиц старше 50 лет и преимущественно женского пола. Заболевание манифестирует как системная воспалительная реакция и системный васкулит с вовлечением в патологический процесс в основном средних и крупных сосудов, отходящих от аорты, в том числе ветвей сонной артерии — глазной и височной. Патогенетически поражение артерий при ГКА представляет собой сочетание аутовоспалительного и аутоиммунного процессов, итогом чего становится ремоделирование стенок сосудов с сужением их просвета и последующим развитием ишемии в пораженных органах и тканях. Одним из нехарактерных прежде симптомов ГКА, который в ряде случаев может предшествовать дебюту основного заболевания, являются кохлеовестибулярные нарушения, и среди них — сенсоневральная тугоухость, которая встречается в 25—60% случаев. Представлен нетипичный клинический случай ГКА, который дебютировал в качестве подострого риносинусита после перенесенной инфекции SARS-Cov-2 и осложнился развитием двустороннего экссудативного среднего отита, что привело к формированию тугоухости смешанного характера глубокой степени. По клиническим проявлениям патологическое состояние напоминало гранулематоз с полиангиитом (ГПА), при этом не было повышения уровней антинейтрофильных цитоплазматических антител в крови пациентки. Идентифицировать заболевание позволила классическая клиническая картина с унилатеральным поражением зрительной функции спустя 12 мес от появления первых симптомов. Безотлагательное привлечение терапии кортикостероидами позволило оперативно купировать как основные симптомы заболевания, так и проявления риносинусита и экссудативного отита, добиться существенного восстановления слуховой функции. Высказано предположение о том, что сочетание поражения среднего и внутреннего уха в данном случае либо могло быть следствием одновременного развития ГПА и ГКА, либо явилось результатом совпадения ряда звеньев патогенеза этих заболеваний, а именно активации B-клеток, а также чрезмерной пролиферации моноцитов/макрофагов, продуцирующих металлопротеиназу-9.

Juvenile-onset mixed connective tissue disease (jMCTD) accounts for 7-23 % of MCTD cases but remains poorly described. We aimed to characterize clinical features, treatments, and outcomes of patients with jMCTD, and compare them to adult-onset MCTD (aMCTD) patients. We conducted a multicenter, retrospective, case-control study within the French MCTD cohort. Each jMCTD patient was compared to 3 matched aMCTD patients. Forty-seven jMCTD patients (93.6 % girls; median age at onset 14 [11-16] years) were included. Forty-four (93.6 %) jMCTD patients fulfilled either Sharp or Kasukawa diagnostic criteria. None of them met other diagnostic criteria without fulfilling Sharp or Kasukawa criteria. At diagnosis, jMCTD patients' main manifestations were Raynaud's phenomenon, arthralgia, and myalgia. jMCTD patients had less frequently puffy fingers than aMCTD (p < 0.0001). Cumulatively, jMCTD patients mainly received glucocorticoids (80.9 %), hydroxychloroquine (95.7 %) and immunosuppressants (93.6 %). They received a higher initial dose of glucocorticoids (30 [20-60] mg/day vs. 15 [10-35] mg/day, p = 0.02), and significantly more frequently methotrexate (Methotrexate) and rituximab (p = 0.01) over time compared to aMCTD. After a median follow-up of 9.8 [6.6-16.2] years, 29 (61.7 %) jMCTD patients were in remission (vs. 62 (44.0 %) aMCTD; p < 0.05), 36 % had progressed to another CTD (vs. 30.5 % aMCTD; p = 0.5), mainly systemic lupus erythematosus, 11 (23.4 %) had developed interstitial lung disease, 2 (4.3 %) pulmonary arterial hypertension, and 1 (2.1 %) died. jMCTD share the same clinical characteristics as aMCTD patients, but less frequently have puffy fingers. Outcomes appear more favorable in jMCTD than aMCTD, with higher remission rates, albeit at the cost of more intensive treatment.

Gain-of-function mutations in the dsDNA sensing adaptor STING lead to a severe autoinflammatory syndrome known as STING-associated vasculopathy with onset in infancy (SAVI). Patients with SAVI develop interstitial lung disease (ILD) and produce autoantibodies that are commonly associated with systemic autoimmune diseases. Mice expressing the most common SAVI mutation, STING V154M (VM), similarly develop ILD but exhibit severe T and B cell lymphopenia and low serum Ig titers, and they lack autoantibodies. Importantly, lethally irradiated VM hosts reconstituted with WT stem cells (WT→VM) still develop ILD. In this study, we find that WT→VM chimeras had restored B cell function, produced autoantibodies, and thereby recapitulated the loss of tolerance seen in patients with SAVI. Lymphocytes derived from both WT and BCR or TCR transgenic (Tg) donors accumulated in the extravascular lung tissue of WT+Tg→VM mixed chimeras, but lymphocyte activation and germinal center formation required WT cells with a diverse repertoire. Furthermore, when T cells isolated from the WT→VM chimeras were adoptively transferred to naive Rag1-deficient secondary hosts, they trafficked to the lung and recruited neutrophils. Overall, these findings indicated that VM expression by radioresistant cells promoted the activation of autoreactive B cells and T cells that then differentiated into potentially pathogenic effector subsets.

The identification of novel, yet easily measurable biomarkers of inflammation and oxidative stress might assist in the diagnosis and management of patients with rheumatic diseases (RDs). We conducted a systematic review and meta-analysis of studies investigating the circulating concentrations of bilirubin, the end product of heme metabolism and a potent endogenous antioxidant with anti-inflammatory properties, in patients with RDs and healthy controls. The electronic databases PubMed, Scopus, and Web of Science were searched from inception to 31 December 2023 for relevant articles. We evaluated the risk of bias and the certainty of evidence using the Joanna Briggs Checklist and the Grades of Recommendation, Assessment, Development, and Evaluation Working Group system, respectively. In 17 eligible studies, all with low risk of bias, compared to controls, patients with RDs had significantly lower concentrations of total bilirubin (standard mean difference, SMD=-0.68, 95% CI -0.91 to -0.44, p<0.001; I2 = 92.5%, p<0.001; low certainty of evidence), direct (conjugated) bilirubin (SMD=-0.67, 95% CI -0.92 to -0.41, p<0.001; I2 = 81.7%, p<0.001; very low certainty of evidence), and the active antioxidant and anti-inflammatory indirect (unconjugated) form of bilirubin (SMD=-0.71, 95% CI -1.18 to -0.24, p=0.003; I2 = 95.1%, p<0.001; very low certainty of evidence). The results of the meta-analysis were stable in sensitivity analysis. In meta-regression, there were no significant associations between the SMD of total bilirubin and several clinical and demographic characteristics, including age, male to female ratio, number of participants, liver enzymes and erythrocyte sedimentation rate. In subgroup analysis, the SMD of total bilirubin was significant across a range of RDs, including rheumatoid arthritis, systemic lupus erythematosus, primary Sjögren syndrome, and myositis. Therefore, the results of our systematic review and meta-analysis suggests that the reductions in bilirubin concentrations observed in patients with RDs reflect a state of impaired antioxidant and anti-inflammatory defence due to bilirubin consumption and highlight the promising role of this endogenous product as a biomarker of RDs. https://www.crd.york.ac.uk/prospero/, identifier CRD42023500649.