The postpartum period represents a critical and underexplored phase in the reproductive course of women with systemic autoimmune diseases (SAD). While advances in disease management have substantially improved pregnancy outcomes, the weeks and months after delivery remain associated with a significant burden of maternal complications. Abrupt immunological and hormonal changes, together with treatment modifications during pregnancy and breastfeeding, may predispose women with SAD to disease reactivation and other adverse outcomes after delivery. This Mini Review summarizes the available evidence on postpartum complications in women with SAD, with a focus on disease flares, thrombotic and infectious events, mental health and quality of life, and therapeutic challenges during lactation. Despite its clinical relevance, postpartum outcomes remain insufficiently investigated, with limited prospective data, heterogeneous endpoints, and gaps between clinical recommendations and real-life practice. Recognizing the postpartum period as a distinct and integral component of reproductive health is essential to improve maternal outcomes and optimize long-term care for women with SAD.

OBJECTIVES:To review the dual impact of hydroxychloroquine (HCQ) on the cardiovascular system, focusing on both its cardioprotective effects and potential cardiotoxicity in patients with autoimmune diseases. METHODS:A structured narrative review of the literature was conducted using PubMed/MEDLINE up to March 2025. Relevant studies including clinical trials, observational studies, mechanistic research, and reviews were selected to summarise the molecular mechanisms and cardiovascular effects of HCQ. RESULTS:HCQ exerts multiple beneficial cardiovascular effects through anti-inflammatory, antithrombotic, metabolic, and endothelial-protective mechanisms. It reduces cytokine production, oxidative stress, platelet activation, and improves lipid and glucose profiles, contributing to decreased cardiovascular risk in patients with systemic autoimmune diseases. However, HCQ may also induce cardiotoxic effects, particularly with long-term use or high cumulative doses. These include QT interval prolongation, conduction abnormalities, and a rare but severe form of cardiomyopathy related to lysosomal dysfunction and impaired autophagy. The risk is higher in patients with advanced age, renal dysfunction, pre-existing heart disease, or concomitant use of QT-prolonging drugs. CONCLUSIONS:HCQ has a complex and context-dependent cardiovascular profile. While generally cardioprotective at standard doses, it may lead to rare but serious cardiac adverse effects in highrisk patients. A risk-adapted monitoring strategy is essential to optimise its benefit-risk balance in clinical practice.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterised by a complex pathogenesis, heterogeneous clinical manifestations and a variable disease course. This review summarises the most relevant contributions on SLE published during 2025, following the framework of the One Year in Review series. In particular, we focus on emerging pathogenetic insights, novel and refined biomarkers, clinical manifestations and outcomes, comorbidities, and evidence from clinical trials and real-world studies, highlighting both recent progress and persistent unmet needs in the management of SLE.

Pregnancy in women with rare vascular diseases is highly challenging, as it can be associated with significant maternal and foetal risks, requiring complex and multidisciplinary management. Care across countries remains insufficiently characterized, and both patients and healthcare providers across Europe highlight the need for better structures and organization to support this critical and potentially life-threatening phase. To describe current practices, perspectives, and challenges faced by patients and healthcare professionals in the management of pregnancy in women with rare vascular diseases. A survey developed by the European Reference Networks (ERN) pregnancy working group was extended with VASCERN-specific questions, resulting in a 13-item questionnaire. The survey was distributed to healthcare providers and patient representatives (ePAGs). Qualitative data from open-ended responses were analysed using an inductive thematic approach. 36 responses were collected from 145 invited VASCERN members, resulting in a 25

OBJECTIVE:To identify different clusters of SLE patients in remission based on patient-reported outcomes (PROs) and clinical factors that predict cluster membership. METHODS:A cross-sectional monocentric study of adult consecutive SLE outpatients in stable clinical remission. Clinical and laboratory data were collected. At enrolment, each patient completed PROs. A hierarchical clustering analysis based on PROs exploring fatigue (Functional Assessment of Chronic Illness Therapy), disease impact (Lupus Impact Tracker), mental and physical health (mental component summary and physical component summary of the Short Form 36) was performed. Logistic regression assessed predictors of cluster membership, adjusting for demographic and clinical variables. RESULTS:195 SLE patients were enrolled. Two distinct clusters emerged: a 'low symptom burden (LSB)' cluster, including 81/195 (41.5%) patients, and a 'high symptom burden (HSB)' cluster, including 114/195 (58.5%) patients. The HSB was characterised by worse scores in all PROs compared with the LSB. The HSB cluster exhibited older age at diagnosis (33.23±11.97 vs 27.75±11.57; p=0.002), less frequent previous renal involvement (33.3% vs 65.4%; p<0.001), more frequent previous neuropsychiatric lupus (17.2% vs 1.3%; p=0.001), more fibromyalgia (26.3% vs 5.3%; p=0.001) and ongoing glucocorticoid use (58.8% vs 37.0%; p=0.004). Fibromyalgia (OR 7.27, 95% CI 2.27 to 29.15, p=0.002) and glucocorticoid treatment (OR 3.05, 95% CI 1.43 to 6.77, p=0.005) were independently associated with higher likelihood of HSB membership; renal involvement was associated with LSB membership (OR 0.23, 95% CI 0.10 to 0.51, p≤0.001). CONCLUSIONS:Among SLE patients in remission, two distinct health-related quality of life phenotypes can be identified: an HSB and an LSB. Fibromyalgia and glucocorticoid treatment emerged as independent predictors of HSB. These findings underline the need to optimise disease management and align treatment goals with patient priorities.

PV221 / #530 Poster Topic:AS23 - SLE-Diagnosis, Manifestations, & Outcomes The assessment of skin involvement in Systemic Lupus Erythematosus (SLE) can represent a challenge for clinicians, not only in the differential diagnosis with other dermatological conditions but also in discerning SLE cutaneous disease activity from damage. This results in a need to optimize the management of SLE patients with mucocutaneous involvement, as the development of skin damage may be early during disease course. Ultra-high frequency ultrasound (UHFUS), with submillimeter resolution, is a promising tool for evaluating superficial structures, finding increasing application in the field of dermatology in recent years. The aim of the study was to explore a possible role of UHFUS assessment in the evaluation of skin involvement in a monocentric cohort of SLE patients. Consecutive adult SLE patients (2019 EULAR/ACR criteria) regularly followed at our Lupus Clinic were prospectively enrolled during a scheduled outpatient visit in presence of skin lesions. Demographical, clinical, serological and treatment data were collected at enrollment. Disease activity and organ damage were evaluated with the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and SLICC/ACR Damage Index (SDI), respectively. Clinical assessment of skin lesions was done by an experienced rheumatologist using the Cutaneous LE Disease Area and Severity Index (CLASI); at the same time, UHFUS evaluation of skin lesions was performed with a 70 MHz probe by an experienced dermatologist. The Skindex-16 questionnaire was used to assess the impact of skin involvement on patients’ quality of life. We included 94 assessments in 59 SLE patients with skin lesions. Cutaneous disease subtypes were distributed as follows: 18/59 acute (30.5%), 8/59 subacute (13.6%), 27/59 chronic (45.8%); a minority of patients had nonspecific skin lesions (10.2%). The characteristics of the cohort are detailed in Table 1. At the clinical evaluation, concomitant presence of active lesions and skin damage was observed in 52/94 cases (55.3%), presence of active skin lesions without damage in 40/94 cases (42.6%), while only skin damage in 2/94 cases (2.1%). The most frequent UHFUS alteration was the presence of power Doppler (68/94, 72.3%), followed by dermal edema (43/94, 45.7%), dermal inhomogeneity (41/94, 43.6%), follicular plugging (37/94, 39.4%), vascular ectasia (30/94, 31.9%), thinning (11/94, 11.7%) and thickening (9/94, 9.6%) of the epidermis. The CLASI activity score was significantly higher in cutaneous areas with power Doppler signal (p= 0.005). Dermal edema was also found to be associated with higher CLASI activity scores, considered both globally (p= 0.004) and at the level of the US-evaluated area (p< 0.001). Skindex-16 symptoms subscale scores were significantly higher in patients with UHFUS findings of power Doppler (p= 0.01) and thinning of the epidermis (p= 0.04). Moreover, we found a positive correlation between CLASI activity and the scores of all Skindex-16 subscales (Rho 0.324,p= 0.002 for symptoms; Rho 0.312,p= 0.003 for emotions; Rho 0.378,p< 0.001 for functioning), also present but weaker between CLASI-Damage and the symptoms (Rho 0.228,p= 0.032) and functioning (Rho 0.275,p= 0.009) domains. Table 1: characteristics of the cohort Our preliminary data demonstrate that UHFUS presence of power Doppler and dermal edema is associated with skin activity clinically assessed by CLASI. These findings suggest that UHFUS may play a role in supporting the clinician in the differential diagnosis between active skin lesions and damage, to optimize the management of skin involvement in SLE.

Pregnancy and family planning for individuals living with rare and low prevalence diseases present unique medical, psychological, and logistical challenges. The European Reference Networks (ERNs) were established to address healthcare disparities and enhance patient care for rare diseases across Europe. The ERN Transversal Working Group on Pregnancy and Family Planning was created to identify common unmet needs and to develop targeted actions to improve healthcare delivery. As part of this initiative, a survey was conducted to gather insights from patients, caregivers, and family members about their experiences and challenges related to pregnancy and family planning. The survey was co-designed by healthcare professionals and patient representatives from 20 ERNs. It covered various domains, including fertility preservation, pre-conceptional counselling, psychological support in the pre-conceptional counselling, pre-implantation diagnosis, prenatal diagnosis, family planning, pregnancy monitoring, post-pregnancy monitoring, lactation and newborn management. The survey, available in multiple languages, was distributed via online platforms between February and July 2022. Quantitative responses were analysed descriptively, while qualitative data from open-ended questions were processed using word frequency analysis. A total of 769 responses were collected, with 574 from patients and 155 from caregivers. The majority of respondents were female (90

BACKGROUND: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. METHODS: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. FINDINGS: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. INTERPRETATION: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. FUNDING:None.

This review highlights key advancements in systemic lupus erythematosus (SLE) research during 2024, covering pathogenesis, novel therapies, biomarkers, and clinical outcomes. Notable findings include new insights into immune dysregulation, promising therapeutic targets, and real-world data confirming the efficacy of anifrolumab and belimumab. Advances in biomarkers enhance disease monitoring, while multidisciplinary approaches improve reproductive outcomes and quality of life. These developments contribute to refining SLE treatment strategies and patient management.

OBJECTIVE:To evaluate the incidence and types of complications occurring within 60 days postpartum in patients with systemic autoimmune diseases (SAD), focusing on disease flares and other clinical events. METHODS:This is a retrospective analysis of prospectively collected data from a single-centre cohort. Variables included demographic and clinical features, pregnancy treatments, disease course, postpartum visit attendance, complications and breastfeeding data. RESULTS:A total of 253 pregnancies were included. Most diagnoses were connective tissue diseases (CTDs, 80.2%), followed by inflammatory arthritis (14.2%) and vasculitis (5.5%). A postpartum visit was performed in 234 patients (92.5%). Postpartum complications occurred in 50 patients (19.8%), including 42 flares (16.6%) and 12 other complications (4.7%). Flares included 20 articular, five mucocutaneous, five renal, four hematological, three parotid swelling, two deep venous thromboses in aPL-positive patients, two uveitis relapses and one myositis. Flares were associated with active disease during pregnancy (P < 0.01). Inflammatory arthritis showed the highest flare rate (41.7% vs 12.0% in CTD, P < 0.01), though severe flares occurred only in CTD or vasculitis. Other complications included six hypertension cases, four postpartum hemorrhages (two on LDA/LMWH), one Clostridium difficile infection and one ICU admission for severe hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. Non-flare complications did not differ by diagnosis. At postpartum visit, 147 patients (58.5%) were breastfeeding. Of the 42 with flares, four were contraindicated to breastfeed due to therapies. The others who did not breastfeed did so by choice or unrelated reasons. CONCLUSIONS:The postpartum period is high-risk in SAD patients. Follow-up should extend beyond pregnancy, with multidisciplinary care to manage disease activity and breastfeeding-related treatment restrictions.

PV238 / #532 Poster Topic:AS23 - SLE-Diagnosis, Manifestations, & Outcomes With the new millennium major changes have occurred in the management of lupus, these encompass the optimization of the use of old drugs, the identification of therapeutic targets such as LLDAS and remission and the introduction of new drugs such as biologics. The aim of the present study was to analyze how the new treatment paradigm impacted on the management of SLE over time in the real-life setting. This is a retrospective observational study on SLE patients regularly followed at our unit and with a follow-up of at least 1 year; patients were divided in 2 groups: group 1 including patients diagnosed between 1980 and 2000 and group 2 those diagnosed after 2000. Demographic characteristics, clinical manifestations at disease onset and cumulative organ involvement, disease activity, organ damage and disease state over time and treatments received were compared. 428 SLE patients were included in the study, 377 females (88%), 143 patients in Group 1 (33.4%) and 285 (66.6%) in group 2. Presenting symptoms were similar between the 2 groups, while over the entire disease course we found a higher frequency of renal involvement (54% vs 40%) and neuropsychiatric involvement (17% vs 6%) in patients diagnosed before 2000. As far as therapy is concerned, almost all patients received GC during their disease course although in group 2 we found 11 patients who did never take GC (4%, p=0.02). Longitudinal analysis of the GC cumulative dose showed similar doses during the first year of the disease; however, at 5 and 10 years after diagnosis group 1 received significantly higher dosages (median 8.7 g vs 7.6 g and 15.35 g vs 14 g respectively, p<0.001 in both analyses). Interestingly, a higher percentage of patients was GC-free at 5 years from diagnosis in the group diagnosed after 2000 (29.4% vs 6.6%). 394 patients received HCQ during the disease course (93.5%), a higher proportion of patients in group 2 although not statistically different (95% vs 90%). The proportion of patients who received at least 1 IS drug within the first year of follow-up was significantly higher in patients diagnosed after 2000 (60.7% vs 39%, p<0.001) Overall, 129 patients received at least on biological drug (30%), with a significantly higher proportion in group 2 (34% vs 22%, p=0.01). In group 2, 22 (8%) patients received a biological treatment within the first year since diagnosis. At 1 year from diagnosis remission resulted more frequently achieved in patients diagnosed after 2000 (57% vs 46% respectively, p=0.03). Overall 9.7% of patients developed at least 1 item of the SLICC/DI within the first year from diagnosis (median SDI=1, range 1-3); 17.7% within 5 years (median SDI= 1, range 1-5) and 32.6% within 10 years (median SDI=1, range 1-6). The median damage score over time was similarly very low in both groups. The occurrence of renal damage (RD), cardiovascular events (CVE) and osteoporotic fractures did not show statistically significant differences between the 2 groups. The study highlights how the clinical management of SLE patients has changed in recent years by incorporating the new treatment paradigm based on the early use of immunosuppressive drugs and steroid-sparing strategies, resulting in more effective disease control.

ObjectivesTo describe different clinical phenotypes of severe flares in a monocentric cohort of SLE patients and to compare treatment and outcomes.Material and methodsRetrospective study of prospectively collected data on 122 severe flares occurred in 110 patients, between 2018 and 2023, and followed up for 12 months after the flare. Baseline characteristics included disease activity assessment by SELENA-SLEDAI and BILAG 2004 scores, demographic and laboratory data. A hierarchical unsupervised segmentation method was applied to cluster flares based on baseline features. Treatments and outcomes according to LLDAS, DORIS Remission and SRI definitions, were compared among clusters at different timepoints.ResultsWe identified 3 clusters, 2 composed mainly by extra-renal, and one by renal flares. Among non-renal clusters, cluster 1 was characterized by severe constitutional symptoms, serositis and arthritis occurring in younger patients, associated with hyper-inflammatory biomarkers and multiple autoantibodies specificities. Cluster 2 included flares with more BILAG B scores and mainly mucocutaneous and musculoskeletal manifestations, and overlapping antiphospholipid syndrome (APS). Cluster 3 was the renal flares cluster. Cluster 1 and the renal cluster were treated more frequently with glucocorticoid (GC) pulses and mycophenolate mofetil (MMF) and presented higher daily and cumulative GCs doses at 12 months (t12). These two clusters also shared similar percentage of attainment of LLDAS (about 50%) and remission (about 35% both) at t12, compared to 73% of LLDAS and 53% of remission in cluster 2 at t12.ConclusionsWe described three different clusters of severe flares in SLE in a real-life setting, identifying a hyper-inflammatory flare phenotype, that shares a comparable proportion of unsatisfying response to treatment as renal flares. Our results may represent a clinical starting point, in the context of precision medicine, for better characterization of severe non-renal disease of SLE, with the final aim of setting up early tailored treatment strategies.

Rare and complex diseases can have a significant impact on family life, and managing the reproductive aspects of patients of childbearing age with rare diseases is often difficult and complex. A European Reference Network (ERN) Transversal Working Group (WG) on Pregnancy and Family Planning was created to join forces to promote and address issues on these topics in rare and low-prevalence diseases. To outline the challenges and the good practices related to pregnancy and family planning in rare and complex diseases for healthcare professionals (HCPs). A survey on state of the art and unmet needs was created by a co-design group of both clinicians and patients’ representatives from 20 ERNs. The survey was uploaded in English on the online platform “EU Survey” and disseminated by respective ERNs and learned societies. Seven transversal domains were explored in the survey by using closed and open-ended questions: fertility preservation, pre-conceptional counselling, family planning counselling, pre-implantation diagnosis, prenatal diagnosis, pregnancy monitoring and post pregnancy monitoring, lactation monitoring/counselling and newborn management. The questions investigated for each topic were the following: level of importance, activities performed by the centre, clinical challenges, good practice and educational activities. A total of 197 answers were collected from 24 different countries. Unmet needs for HCPs included: the need to improve communication between different HCPs, the lack of predefined organizational pathways, the lack of availability of expert HCPs for some pregnancy-related issues and the need to streamline the care provided among different countries. In addition, the survey underlined the need to improve the educational activities provided to rare disease patients. Physicians and patients need to be educated on the emerged unmet needs in order to standardize the information for both HCPs and patients with rare diseases. Educational activities should be considered to help to disseminate information.

AbstractSystemic lupus erythematosus, antiphospholipid syndrome, and rheumatoid arthritis are chronic autoimmune diseases affecting women of childbearing age. These diseases may impair fertility and fecundity, as well as complicate pregnancy and the puerperium in these patients including disease flare and obstetric complications on both the maternal and fetal side. For each patient, an appropriate preconceptional counseling with risk stratification is required, including assessment of disease activity, organ involvement, serological profile, and comorbidities.In cases of pregnancy, the aims of treatment are to prevent disease activity, to treat disease activity in cases of flare, and to prevent maternal and fetal complications such as preeclampsia or fetal loss. In all patients with these diseases, close clinical monitoring during pregnancy and puerperium is mandatory. This review aims to summarize the fertility issues in patients with systemic lupus erythematosus, antiphospholipid syndrome, and rheumatoid arthritis and to provide an update on pregnancy management and outcomes in these patients.

Background: Patients diagnosed with Systemic Autoimmune Diseases (SAD) face distinct challenges during pregnancy potentially affecting maternal health and neonatal outcomes. Despite the well-known prominence of sleep and mental health disturbances in SAD and the vulnerability of mental health during pregnancy due to physiological, psychological, and hormonal changes, a significant gap persists in comprehending the prevalence, severity, and intricate interrelationships between sleep disturbances, anxiety, and depression symptoms in SAD during gestation. Objectives: To investigate the prevalence of insomnia, anxiety, and depression symptoms in individuals with SAD during pregnancy. Additionally, this study evaluates the correlation between mood, anxiety, and insomnia, providing insights into the complex interrelationships among these factors. Methods: This study assessed consecutive women during pregnancy diagnosed with SADs, including Connective Tissue Diseases (CTD), Inflammatory Arthritis (IA) and Systemic Vasculitis (SV) attending the pregnancy clinic of a tertiary referral center. Patients were evaluated through the Insomnia Severity Index (ISI), the State-Trait Anxiety Inventory (STAI Y1 and Y2), the Difficulties in Emotion Regulation Scale (DERS), the Mood Disorder Questionnaire (MDQ), and the Postpartum Depression Predictors Inventory-Revised (PDPI-R). Frequency analyses identified the prevalence of patients reporting significant symptoms (scores over the cut-point in the referred questionnaires). Non-parametric between group comparisons and correlations were used to evaluate the associations between clinical variables (diagnosis, pharmacological treatment, years between disease onset and pregnancy) and insomnia, mood, and anxiety symptoms with a significance level set at p-value <0.05. Results: Sixty-five patients were enrolled, with a mean age of 34.69 (±4.57) years and a mean disease duration of 9 (±5.10) years. Fifty patients (76.9%) were diagnosed with Connective Tissue Diseases (CTD), 20 (18.5%) with Inflammatory Arthritis (IA), and 3 (4.6%) with Systemic vasculitis (SV). Among the patients, 13 (22.8%) were receiving glucocorticoids (GCs), 33 (56.9%) hydroxychloroquine (HCQ), 9 (15.3%) traditional or biologic immunosuppressants (IS TRAD/BIO), and 29 (49.2%) anticoagulants or antiplatelet agents (ACT/APT). A high percentage of significant symptoms was found with prevalence rates of insomnia at 53.1%, anxiety symptoms at 45.3% (state) and 40.6% (trait), emotional regulation difficulties at 44.6%, significant mood disturbances at 10.8%, and a significant risk of postpartum depression in 6.2% of cases. Between-group comparisons based on diagnostic categories and pharmacological treatments revealed significant differences when patients were categorized according to hydroxychloroquine (HCQ) intake with significantly higher STAI-Y1 and PDPI-R scores in the group not consuming HCQ compared to the group consuming HCQ (p-value <0.05, see Table 1). Significant correlations were found between the STAI and ISI, MDQ and DERS scores (p <0.05, see Table 2). Conclusion: This study sheds light on the underexplored psychological aspects of pregnancy in SAD, emphasizing the need for comprehensive mental health care in this population. Significant correlations between anxiety symptoms and mood, emotion regulation and insomnia suggest the necessity to further explore the role of anxiety as a trigger of mental health complications in this clinical population. The association emerged between the HCQ use and better scores in terms of anxiety symptoms and post-partum depression is intriguing. We could argue that HCQ may maintain better control over the underlying autoimmune condition thus influencing mental health outcomes during pregnancy. These are preliminary interpretations, and further research, including controlled studies and exploration of potential confounding factors, is needed to establish causation and understand the underlying mechanisms. REFERENCES: NIL. Table 2. Correlations between questionnaires total scores and age and disease duration in the overall sample Acknowledgements: NIL. Disclosure of Interests: None declared.

Objectives To describe phenotypes and outcomes of extra-renal flares in SLE, to identify clusters of extra-renal flares based on baseline features, and to develop a machine learning (ML) tool capable of predicting 'difficult to treat' (D2T) flares. Methods Extra-renal flares that occurred in our cohort over the last five years with at least one year of follow-up were included. Baseline clinical variables were described and flares assigned to clusters. Attainment of remission and low disease activity state (LLDAS) at 12 months were compared. Flares were then considered 'D2T' in case of non-attainment of LLDAS at 6 and 12 months. Baseline features were used to train a ML model able to predict future D2T-flares, at admission. Traditional approaches were then compared with informatic techniques. Results Among 420 SLE patients of the cohort, 114 flares occurred between 2015 and 2021; 79 extra-renal flares, predominantly mucocutaneous (24.1%) and musculoskeletal (45.6%), were considered. After 12 months, 79.4% and 49.4% were in LLDAS and in remission, respectively, while 17 flares were classified as D2T (21.5%); D2T flares received a higher cumulative and daily dose of glucocorticoids. Among the clusters, cluster 'D' (mild-moderate flares with mucocutaneous manifestations in patients with history of skin involvement) was associated with the lowest rate of remission. Among clinical data, not being on LLDAS at 3 months was the unique independent predictor of D2T flares. Conclusions Our clusterization well separates extra-renal flares according to their baseline features and may propose a new identification standard. D2T flares, especially refractory skin manifestations, are frequent in SLE and represent an unmet need in the management of the disease as they are associated with higher glucocorticoid (GC) dosage and risk of damage accrual. Our ML model could help in the early identification of D2T flares, flagging them to elevate the attention threshold at admission.

Systemic lupus erythematosus (SLE) is classically regarded as the landmark of systemic autoimmune diseases, characterised by protean, multi-systemic manifestations and a highly variable clinical course.Over the last years, both clinical and translational clinical research efforts led to significant steps forward in management and treatment of SLE. However, numerous aspects of SLE, from pathogenesis to treatment, still remain challenging, and several unmet needs persist for both patients and physicians. Following the previous annual reviews of this series, herewith, we aim to report the most relevant new updates on SLE, issued in 2023. In particular, we focused on biomarkers, clinical aspects and outcomes, comorbidities, as well as new treatment targets and real-world evidence.

Background: C-Reactive Protein (CRP) elevation in SLE is considered as strongly suggestive of infection. In clinical practice, however, it is not uncommon to observe an increase of inflammatory biomarkers related to SLE disease activity, namely to arthritis and serositis. Objectives: To characterize severe SLE flares with hyper-inflammatory stigmata and to compare them to severe, no-hyper-inflammatory flares. Methods: This is a retrospective analysis of prospectively collected data about severe disease flares occurred in the last five years in a monocentric cohort of SLE inpatients fulfilling 2019 ACR/EULAR classification criteria. In all cases concomitant infections, hematological or oncological conditions were excluded.The following data were collected from clinical charts: demographics, comorbidities, disease duration, cumulative organ involvement and damage accrual (SLICC-DI), disease activity (SLEDAI 2K, BILAG 2004), immunological profile, laboratory, imaging, histology, and treatment data at the time of the flare (T0), treatment and disease status at 3-, 6- and 12-months of follow-up.Hyper-inflammatory (HI) flares were defined by CRP serum levels ≥ 5 mg/dL and/or circulating ferritin levels ≥ 500 µg/L and were compared with flares without HI characteristics (no-HI), hospitalized in the same period in our Centre.Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. Results: Among 122 severe flares hospitalized in the study period, based on the previously defined criteria, 22 flares, in 21 patients, were HI flares while 100, in 89 patients, were no-HI flares. No patient was found to belong to both groups. Patient and flare characteristics are summarized in Table 1.HI flares presented more frequently fever, pericarditis, arthritis and large vessels vasculitis and less frequently renal involvement, according to SLEDAI definitions. Lymphadenopathies and splenomegaly were also significantly associated with HI flares. According to the BILAG index, patients in the HI group presented more frequently a BILAG A score in the constitutional, cardiopulmonary, and hematological domains.As for laboratory data HI flares showed significantly higher levels of all the inflammatory biomarkers and higher C3 complement levels. Moreover, patients in the HI group presented more frequently a Lupus anticoagulant (LAC) positivity.At the multivariate analysis, cardiopulmonary, constitutional, and hematological involvement, splenomegaly, LAC+ and higher levels of fibrinogen confirmed to be independently associated with the HI phenotype (Table 2).Having a HI flare resulted significantly associated with an overall higher number of diagnostic procedures performed and to a longer duration of hospitalization.With exception of colchicine, no other significant differences were found with respect to therapeutic choices (Table 3); achievement of treatment targets at the different time-points and damage accrual at 12 months was also similar in the 2 subgroups. Conclusion: We identified a subgroup of SLE flares that defines a “hyper-inflammatory” phenotype whose severity seems to be mainly driven by marked constitutional symptoms. Interestingly, HI flares were associated with an underlying large vessels vasculitis in 3 cases.HI flares may represent a challenge for rheumatologists, particularly for the difficulty in differential diagnosis with infections and hematological conditions, leading to a higher number of diagnostic procedures and a longer duration of hospitalization. In view of the association with large vessel vasculitis, the clinician should consider performing a PET-CT scan in patients with HI phenotype to properly establish immunosuppressive therapy.This work suggests that severe SLE flares may present with proteiform and unexpected clinical characteristics. Further studies are needed to better outline clinical phenotypes, from “bedside to bench”, looking for new biomarkers and tailored treatment strategies. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.