Longterm Outcomes and Damage Accrual in Patients with Childhood Systemic Lupus Erythematosus with Psychosis and Severe Cognitive Dysfunction

Objective.(1) To describe the clinical course and response to treatment; and (2) to evaluate and compare damage accrual of distinct phenotypic subgroups of patients with clinically important psychiatric illness of pediatric systemic lupus erythematosus (pSLE).Methods.A single-center cohort study of patients with pSLE followed at a pediatric lupus clinic from 1985 to July 2009. Clinical course and response to treatment were studied. Remission was defined by absence of psychiatric/cognitive symptoms while receiving minimal doses of prednisone. Disease activity and damage were measured using SLE Disease Activity Index and SLE Damage Index.Results.Fifty-three children were included: 40 with psychosis and cognitive dysfunction (PSYC group) and 13 with isolated cognitive dysfunction (COG group). All received immunosuppressive treatment. Eighteen of 32 treated with azathioprine required a change to cyclophosphamide for poor response but none on cyclophosphamide required a change. The median times to remission were 72 weeks (PSYC) and 70 weeks (COG). Eight patients (7 PSYC, 1 COG) experienced flare following response/remission. New damage was noted in 50% of children at a median of 11 months: 57% of PSYC group, 31% of COG group. Persistent cognitive dysfunction was seen in 16% of PSYC patients and 15% of COG patients.Conclusion.Most patients responded to immunosuppressive treatment, although median time to remission was > 1 year. Roughly half the patients acquired a new damage item, most of which did not interfere with functional abilities. Fewer than 20% of patients developed neuropsychiatric damage. Both phenotypes of psychiatric pSLE responded equally well to current treatment.

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Measuring Disease Activity and Damage with Validated Metrics: A Systematic Review on Mortality and Damage in Systemic Lupus Erythematosus

The Journal of Rheumatology ◽

10.3899/jrheum.171310 ◽

2018 ◽

Vol 45 (10) ◽

pp. 1448-1461 ◽

Cited By ~ 5

Author(s):

Stephanie O. Keeling ◽

Ben Vandermeer ◽

Jorge Medina ◽

Trish Chatterley ◽

Tatiana Nevskaya ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Activity Index ◽

Damage Index ◽

Disease Activity Index ◽

Evaluation Methodology ◽

Systemic Lupus ◽

Increased Risk ◽

Damage Accrual

Objective.To identify the effect of disease activity and damage, measured by validated indices, on mortality and damage accrual, in order to inform upcoming Canadian systemic lupus erythematosus (SLE) recommendations.Methods.Following GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology to fill in evidence-to-decision tables to create recommendations for “minimal investigations needed to monitor SLE patients at baseline and subsequent visits,” a systematic literature review was performed. The effect of disease activity and damage, measured by validated metrics, on mortality and damage was systematically reviewed, with metaanalyses performed when available.Results.A title/abstract screen of 5599 articles identified 816 articles for full paper review, with 102 meeting inclusion criteria and 53 with extractable data. Thirty-three articles describing outcomes related to disease activity and 20 articles related to damage were identified. Mortality was associated with higher SLE Disease Activity Index-2000 scores in 6 studies (HR 1.14, 95% CI 1.06–1.22) and higher Systemic Lupus International Collaborating Clinics/ACR Damage Index scores in 6 studies (HR 1.53, 95% CI 1.28–1.83). Higher SLE Activity Measure scores were associated with increased risk of damage in 3 studies (OR 1.06, 95% CI 1.04–1.08). British Isles Lupus Assessment Group was associated with mortality in 1 study with HR of 1.15.Conclusion.Active SLE disease and damage are associated with and predict greater mortality and damage. The use of validated disease activity and damage metrics is important in the assessment of disease activity and damage and will inform upcoming Canadian recommendations for the assessment of SLE.

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The SLICC/ACR Damage Index (SDI) may predict adverse obstetric events in patients with systemic lupus erythematosus

Lupus ◽

10.1177/09612033211045061 ◽

2021 ◽

Vol 30 (12) ◽

pp. 1966-1972

Author(s):

Marcela Ignacchiti Lacerda ◽

Guilherme Ribeiro Ramires de Jesús ◽

Flávia Cunha dos Santos ◽

Nilson Ramires de Jesús ◽

Roger Abramino Levy ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Neonatal Intensive Care ◽

Damage Index ◽

Adverse Outcomes ◽

Neonatal Outcomes ◽

Systemic Lupus ◽

Irreversible Damage ◽

Damage Accrual

Objective The objective of this study was to evaluate the potential impact of irreversible damage accrual in women with systemic lupus erythematosus (SLE) and adverse maternal and/or fetal/neonatal outcomes. Methods Retrospective cohort study with SLE pregnant patients was carried out from January 2011 to January 2020 at the Hospital University Pedro Ernesto (HUPE) of the State University of Rio de Janeiro, Brazil. Irreversible damage was defined according to SLICC/ACR damage index (SDI). The association of SDI on pregnancy outcomes was established by univariate and multivariate regression models and included demographic and clinical variables. Results This study included data from 260 patients in their first pregnancies after SLE diagnosis, with a quarter of them (67/260) scoring one or more points on SDI at the beginning of prenatal care. These patients presented more frequently adverse maternal events, namely, disease activity during pregnancy ( p = 0.004) and puerperium ( p = 0.001), active lupus nephritis ( p = 0.04), and hospitalizations ( p = 0.004), than those with no SDI score. Similarly, the risks of adverse fetal and neonatal outcomes were also higher among the patients with SDI ≥ 1 (59.7% vs 38.3% p = 0.001) even after controlling data for disease activity (SLEPDAI > 4). Patients with SDI ≥ 1 presented more frequently preterm deliveries (46.3% vs 31.6%; p = 0.01), small for gestational age infants (28.3% vs 18.1%; p = 0.04), and neonatal intensive care unit admission (26.9% vs 1.5%; p < 0.001). The multivariate analyses showed that SDI ≥ 1 is an independent risk factor for hospitalization due to obstetric complications ( p = 0.0008) and preterm delivery ( p = 0.009). Conclusion Pregnant SLE patients who present irreversible damage accrual may have higher risk of maternal and fetal adverse outcomes, independently of disease activity. These results should be validated in further prospective studies.

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Osteopontin and Disease Activity in Patients with Recent-onset Systemic Lupus Erythematosus: Results from the SLICC Inception Cohort

The Journal of Rheumatology ◽

10.3899/jrheum.180713 ◽

2019 ◽

Vol 46 (5) ◽

pp. 492-500 ◽

Cited By ~ 1

Author(s):

Lina Wirestam ◽

Helena Enocsson ◽

Thomas Skogh ◽

Leonid Padyukov ◽

Andreas Jönsen ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Renal Involvement ◽

Damage Index ◽

Organ Damage ◽

Inception Cohort ◽

Systemic Lupus ◽

Recent Onset ◽

Damage Accrual

Objective.In cross-sectional studies, elevated osteopontin (OPN) levels have been proposed to reflect, and/or precede, progressive organ damage and disease severity in systemic lupus erythematosus (SLE). We aimed, in a cohort of patients with recent-onset SLE, to determine whether raised serum OPN levels precede damage and/or are associated with disease activity or certain disease phenotypes.Methods.We included 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who had 5 years of followup data available. All patients fulfilled the 1997 American College of Rheumatology (ACR) criteria. Baseline sera from patients and from age- and sex-matched population-based controls were analyzed for OPN using ELISA. Disease activity and damage were assessed at each annual followup visit using the SLE Disease Activity Index 2000 (SLEDAI-2K) and the SLICC/ACR damage index (SDI), respectively.Results.Compared to controls, baseline OPN was raised 4-fold in SLE cases (p < 0.0001). After relevant adjustments in a binary logistic regression model, OPN levels failed to significantly predict global damage accrual defined as SDI ≥ 1 at 5 years. However, baseline OPN correlated with SLEDAI-2K at enrollment into the cohort (r = 0.27, p < 0.0001), and patients with high disease activity (SLEDAI-2K ≥ 5) had raised serum OPN (p < 0.0001). In addition, higher OPN levels were found in patients with persistent disease activity (p = 0.0006), in cases with renal involvement (p < 0.0001) and impaired estimated glomerular filtration rate (p = 0.01).Conclusion.The performance of OPN to predict development of organ damage was not impressive. However, OPN associated significantly with lupus nephritis and with raised disease activity at enrollment, as well as over time.

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AB0447 IRREVERSIBLE ORGAN DAMAGE IN PERI- AND POSTMENOPAUSAL WOMEN WITH SYSTEMIC LUPUS ERYTHEMATOSUS IN REMISSION

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2420 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1522.2-1522

Author(s):

S. Shkireeva ◽

E. Zotkin ◽

O. Lesnyak

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Postmenopausal Women ◽

Lupus Erythematosus ◽

Damage Index ◽

Osteoporotic Fractures ◽

Organ Damage ◽

Systemic Lupus ◽

Low Disease Activity ◽

Damage Accrual

Background:Although the survival of patients with systemic lupus erythematosus (SLE) has improved, irreversible organ damage remains a critical concern. Long-standing inflammation, drug-related side effects and comorbidities may eventually cause permanent organ damage even in remission[1].Objectives:To describe irreversible organ damage in peri- and postmenopausal women with SLE in remission and low disease activity, to find predictors of damage progression.Methods:234 peri- and postmenopausal women with SLE were included (mean age 49,94±9,1 years) in our study. All women were under outpatient observation in St.Petersburg State Clinical Rheumatology Hospital #25 (Russia). Mean disease duration was 8,9±7,5 years. We analyzed treatment regimens and doses of glucocorticoids (GC) based on source medical documents. To assess disease activity, we used SLEDAI-2K and LLDAS. To assess organ damage, we used SLICC damage index (SDI).Results:94,3% of women have been taking GC during our study. Median of maintenance dose was 12,5 mg per day. Almost a half of all women (44,8%, n=105) in our study were postmenopausal (mean duration of menopause was 11,1±7,1 years). A half of all patients had low disease activity (44,4%, n=111) or were in remission (18,8%, n=44) according to SLEDAI-2K. 26,5% (n=65) of patients had all 5 criteria and 45,1 % (n=115) of patients had 4 of 5 criteria according to LLDAS. Critical organ damage (SDI>4) was observed in 68,8% (n=161) of women with SLE. Moderate (1≤SDI≤4) and low (SDI=1) damage had 25,6% (n=60) and 6,4% (n=15) of patients respectively. Musculoskeletal damage was on the first place among others: 37,6% (n=88) of patients had osteoporosis with fractures and 34,2% (n=80) had muscle weakness. In 75 women with SLE of osteoporotic fractures occurred in remission or low disease activity (LLDAS). Progression of irreversible organ damage in remission or low disease activity (LLDAS) had 62% (n=145) of women with SLE. Multifactorial logistic regression analysis of factors associated with organ damage in SLE showed that only patients age (р=0.013215), cumulative dose of GC (р=0.000047) and therapy with cyclophosphamide (р=0.041505) were statistically significant.Conclusion:Progression of irreversible organ damage in peri- and postmenopausal women with SLE may occur despite remission or low disease activity. There are no doubts that organ damage accrual is associated with CG therapy. Correction of GC dose or discontinuation of GC treatment in remission can predict organ damage accrual in SLE including osteoporosis and osteoporotic fractures.References:[1]Frodlund M, Reid S, Wetterö J, Dahlström Ö, Sjöwall C, Leonard D. The majority of Swedish systemic lupus erythematosus patients are still affected by irreversible organ impairment: factors related to damage accrual in two regional cohorts. Lupus. 2019;28(10):1261–1272. doi:10.1177/0961203319860198Disclosure of Interests:None declared

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Systemic Lupus Erythematosus in a Multiethnic US Cohort (LUMINA): LXI. Value of C-Reactive Protein as a Marker of Disease Activity and Damage

The Journal of Rheumatology ◽

10.3899/jrheum.080175 ◽

2008 ◽

Vol 35 (12) ◽

pp. 2355-2358 ◽

Cited By ~ 30

Author(s):

ANAM. BERTOLI ◽

LUIS M. VILÁ ◽

JOHN D. REVEILLE ◽

GRACIELA S. ALARCÓN

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Multivariable Analysis ◽

Damage Index ◽

C Reactive Protein ◽

Systemic Lupus ◽

Reactive Protein ◽

Damage Accrual ◽

Hs Crp

ObjectiveTo determine whether C-reactive protein (CRP) measured by a high sensitivity (hs) assay is a surrogate marker of disease activity and damage in systemic lupus erythematosus (SLE).MethodsFive hundred eighty-eight patients with SLE participating in a multiethnic cohort (Hispanic, African American, and Caucasian) were studied. Disease activity was measured with the Systemic Lupus Activity Measure-Revised (SLAM-R) and damage with the Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI). hs-CRP was measured by immunometric assay. Disease activity and hs-CRP were measured at enrollment and damage accrual at last visit. The association of hs-CRP with the SLAM-R and SDI was examined by univariable (Pearson’s correlation) and multivariable (linear regression) analyses. The association of hs-CRP and each individual domain of the SLAM-R and SDI was examined by Spearman’s correlation.Resultshs-CRP was associated with the SLAM-R in the univariable (r = 0.35, p < 0.001) and multivariable (t = 7.11, coefficient β = 0.27, p < 0.001) analyses. It also correlated with the constitutional, eye, pulmonary, gastrointestinal, neuromotor, and laboratory domains of the SLAM-R. hs-CRP was associated with the SDI (r = 0.12, p = 0.004) in the univariable analysis but not in the multivariable analysis. When the individual domains of the SDI were analyzed, hs-CRP correlated with the renal, pulmonary, cardiovascular, musculoskeletal, and diabetes domains.Conclusionhs-CRP was associated with disease activity but not with overall damage accrual; however, it correlated with specific domains of the damage index. hs-CRP may be useful to monitor the course of the disease and predict its intermediate outcome, but longitudinal studies with serial hs-CRPmeasurements are necessary to define its clinical value.

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Clinical and serological associations of autoantibodies in patients with systemic lupus erythematosus

Journal of Investigative Medicine ◽

10.1136/jim-2021-001887 ◽

2021 ◽

pp. jim-2021-001887

Author(s):

María Correa-Rodríguez ◽

Gabriela Pocovi-Gerardino ◽

Jose Luis Callejas-Rubio ◽

Raquel Ríos-Fernández ◽

María Martín-Amada ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Activity Index ◽

Damage Index ◽

Disease Activity Index ◽

Systemic Lupus Erythematosus Disease ◽

Systemic Lupus ◽

Damage Accrual ◽

Dsdna Antibodies

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the formation of antigen–antibody complexes which trigger an immune response. We investigate certain autoantibodies including nucleosome, double-stranded DNA (dsDNA), Smith, ribonucleoprotein, and Sjögren’s syndrome-related antigens, and examine their associations with disease activity, damage accrual, and SLE-related clinical and serological manifestations in patients with SLE. We conducted a cross-sectional study with a total 293 patients (90.4% female, mean age 46.87±12.94 years) and used the Systemic Lupus Erythematosus Disease Activity Index 2000 and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) to evaluate disease activity and disease-related damage, respectively. Systemic Lupus Erythematosus Disease Activity Index scores were significantly higher in anti-nucleosome-positive (3.87±2.72 vs 2.52±2.76, p=0.004) and anti-dsDNA-positive (3.08±2.91 vs 2.04±2.48, p=0.010) patients compared with patients without these antibodies. SDI scores were also significantly higher in anti-nucleosome-positive patients (1.61±1.99 vs 0.89±1.06, p=0.004). The presence of antinucleosome (p=0.019) and anti-dsDNA antibodies (p=0.001) both correlated significantly with the incidence of nephritis; anti-La antibodies were associated with arthritis (p=0.022), and we also observed a relationship between the presence of antinucleosome antibodies and leukopenia (p=0.011). Patients with antinucleosome or anti-dsDNA antibodies had a higher disease activity and were likely to have nephritis. Antinucleosome was also associated with more damage accrual. A greater understanding of these autoantibodies could lead to the development of new approaches to more accurate assessments of SLE.

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Clinical features, damage accrual, and survival in patients with familial systemic lupus erythematosus: data from a multi-ethnic, multinational Latin American lupus cohort

Lupus ◽

10.1177/0961203320935184 ◽

2020 ◽

Vol 29 (9) ◽

pp. 1140-1145

Author(s):

Rosana Quintana ◽

Guillermo J Pons-Estel ◽

Karen Roberts ◽

Mónica Sacnún ◽

Rosa Serrano ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Clinical Features ◽

Latin American ◽

Lupus Erythematosus ◽

Activity Index ◽

Damage Index ◽

Systemic Lupus ◽

Damage Accrual ◽

Familial Lupus

Objectives This study aimed to compare the clinical features, damage accrual, and survival of patients with familial and sporadic systemic lupus erythematosus (SLE). Methods A multi-ethnic, multinational Latin American SLE cohort was studied. Familial lupus was defined as patients with a first-degree SLE relative; these relatives were interviewed in person or by telephone. Clinical variables, disease activity, damage, and mortality were compared. Odds ratios (OR) and 95% confidence intervals (CI) were estimated. Hazard ratios (HR) were calculated using Cox proportional hazard adjusted for potential confounders for time to damage and mortality. Results A total of 66 (5.6%) patients had familial lupus, and 1110 (94.4%) had sporadic lupus. Both groups were predominantly female, of comparable age, and of similar ethnic distribution. Discoid lupus (OR = 1.97; 95% CI 1.08–3.60) and neurologic disorder (OR = 1.65; 95% CI 1.00–2.73) were significantly associated with familial SLE; pericarditis was negatively associated (OR = 0.35; 95% CI 0.14–0.87). The SLE Disease Activity Index and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) were similar in both groups, although the neuropsychiatric (45.4% vs. 33.5%; p = 0.04) and musculoskeletal (6.1% vs. 1.9%; p = 0.02) domains of the SDI were more frequent in familial lupus. They were not retained in the Cox models (by domains). Familial lupus was not significantly associated with damage accrual (HR = 0.69; 95% CI 0.30–1.55) or mortality (HR = 1.23; 95% CI 0.26–4.81). Conclusion Familial SLE is not characterized by a more severe form of disease than sporadic lupus. We also observed that familial SLE has a higher frequency of discoid lupus and neurologic manifestations and a lower frequency of pericarditis.

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Risk factors for irreversible organ damages in peri- and postmenopausal women with systemic lupus erythematosus

Modern Rheumatology Journal ◽

10.14412/1996-7012-2018-4-89-94 ◽

2018 ◽

Vol 12 (4) ◽

pp. 89-94

Author(s):

S. Yu. Shkireeva ◽

E. G. Zotkin ◽

O. M. Lesnyak

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Postmenopausal Women ◽

Lupus Erythematosus ◽

Maintenance Dose ◽

Activity Index ◽

Damage Index ◽

Systemic Lupus ◽

Irreversible Damage ◽

Damage Accrual

Objective: to identify irreversible organ damages and factors influencing their development and to compare existing musculoskeletal injuries with the activity of systemic lupus erythematosus (SLE).Patients and methods. The investigation enrolled 197 peri- and postmenopausal female outpatients (mean age, 50.94±9.1 years) with SLE, who were followed up at Clinical Rheumatology Hospital Twenty-Five, Saint Petersburg. The mean disease duration was 9.7±7.5 years. Cytostatic and glucocorticoid (GC) treatment regimens and dosages in the examinees were analyzed on the basis of their primary medical records. The investigators assessed the current disease activity by the SLE Disease Activity Index (SLEDAI-2K) and the Lupus Low Disease Activity State (LLDAS) and irreversible organ damages by the Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (DI).Results and discussion. 93.4% of the patients continued to receive GS therapy at the time of inclusion in the study. The median GS maintenance dose was 12.5 mg/day. Almost half of the patients (n=86/43.7%) were in menopause (its mean duration was 12.8±7.1 years). Half of the examinees were noted to have remission (n=36/18.3%) or low SLE activity (n=92/46.7%) according to the SLEDAI-2K. Fifty-seven (28.9%) patients met all 5 LLDAS criteria; at the same time other 96 (48.7%) patients met 4 out of the 5 criteria, the 5th criterion being a high GC maintenance dose. High DI scores of ≥4 were found in two thirds (n=131/66.5%) of the examinees. Musculoskeletal system injuries ranked first among other disorders: osteoporosis (OP) and muscle weakness were detected in 76 (38.6%) and 69 (35.0%) patients, respectively. Regression analysis involving all statistically significant factors showed that the degree of damage was influenced by age (p=0.013215), total GS dose (p=0.000047), and previous therapy with cyclophosphamide (p=0.041505).Conclusion. The contribution of GS therapy to irreversible damage accrual is obvious in peri- and postmenopausal women with SLE. Timely dose adjustment or complete withdrawal of GS during remission in SLE is one of the key factors that substantially reduce the risk of progression of irreversible organ damages due to the prevention of OP and osteoporotic fractures in these patients.

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Assessment of Quality of Life (QoL) in Systemic Lupus Erythematosus Patients at a Tertiary Care Hospital in Egypt

Current Rheumatology Reviews ◽

10.2174/1573397115666190118144903 ◽

2019 ◽

Vol 15 (4) ◽

pp. 304-311

Author(s):

Mervat E. Behiry ◽

Sahar A. Ahmed ◽

Eman H. Elsebaie

Keyword(s):

Quality Of Life ◽

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Tertiary Care ◽

Damage Index ◽

Life Questionnaire ◽

Care Hospital ◽

Systemic Lupus

: Systemic Lupus Erythematosus (SLE) has a profound impact on quality of life. Objective: The objective of this study was to explore the quality of life among Egyptian SLE patients and to assess its relationships with demographic and clinical features. Methods: One hundred sixty-four SLE patients were recruited for this study. Demographic information; clinical parameters; disease activity, as evaluated by the systemic lupus erythematosus Disease Activity Index; and organ damage, as assessed by the systemic lupus international Collaborative Clinics/American College of Rheumatology Damage Index, were reported. Quality of life was assessed with a quality of life questionnaire specifically designed for patients with systemic lupus erythematosus; the questions are grouped in the following six domains: physical function, sociooccupational activities, symptoms, treatment, mood, and self-image. Higher values indicate poorer quality of life. Conclusion: Poor quality of life among Egyptian SLE patients and disease activity are strongly related to impaired lifestyles in these patients.

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The Main Challenges in Systemic Lupus Erythematosus: Where Do We Stand?

Journal of Clinical Medicine ◽

10.3390/jcm10020243 ◽

2021 ◽

Vol 10 (2) ◽

pp. 243

Author(s):

Matteo Piga ◽

Laurent Arnaud

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Systemic Disease ◽

Unmet Need ◽

Clinical Manifestations ◽

New Drugs ◽

Systemic Lupus ◽

Major Step ◽

Damage Accrual

Systemic lupus erythematosus (SLE) is an immune-mediated multi-systemic disease characterized by a wide variability of clinical manifestations and a course frequently subject to unpredictable flares. Despite significant advances in the understanding of the pathophysiology and optimization of medical care, patients with SLE still have significant mortality and carry a risk of progressive organ damage accrual and reduced health-related quality of life. New tools allow earlier classification of SLE, whereas tailored early intervention and treatment strategies targeted to clinical remission or low disease activity could offer the opportunity to reduce damage, thus improving long-term outcomes. Nevertheless, the early diagnosis of SLE is still an unmet need for many patients. Further disentangling the SLE susceptibility and complex pathogenesis will allow to identify more accurate biomarkers and implement new ways to measure disease activity. This could represent a major step forward to find new trials modalities for developing new drugs, optimizing the use of currently available therapeutics and minimizing glucocorticoids. Preventing and treating comorbidities in SLE, improving the management of hard-to-treat manifestations including management of SLE during pregnancy are among the remaining major unmet needs. This review provides insights and a research agenda for the main challenges in SLE.

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